Physiologist, Dr. med. Sciences (1959), Professor (1960), Honored. scientist of the RSFSR (1973), corresponding member. AMN (1980); Prize named after M.P. Konchalovsky AMS (1980). He graduated from medical school in 1941. Faculty of the 1st MMI. In 1941-1945. - in the active army: junior regiment doctor; After being seriously wounded, he was declared unfit for military service. service; voluntarily remained in the army: resident (1942-1944), head of the front-line evacuation hospital (1944-1945). In 1945-1949 - postgraduate student of the Academy of Medical Sciences, 1949-1950. - scientific employee, 1950-1958 - manager physiol. Laboratory of the Research Institute of Tuberculosis of the Ministry of Health of the RSFSR; in 1958-1960 - Professor, 1960-1988 - manager Department of Normal Physiology 2nd MMI. G.I. Kositsky is the author and director of priority research on various problems of experimental cardiology and the study of the role of the nervous system in regulating the reactivity of the body. Gave a theoretical basis for the sound method of studying blood pressure; established the causes of the occurrence of “Korotkoff sounds”, studied the mechanisms of the so-called. anomalies of Korotkov sound phenomena, which made it possible to obtain additional diagnostic data for assessing the state of the cardiovascular system. Joint with M.G. Udelnov and I.A. Chervovoy proved the existence of true intracardiac peripheral reflexes; established the role of the intracardiac nervous system in the regulation of systemic circulation and the mechanisms of its interaction. He substantiated the important role of the afferent nerves of the heart in the development of pathology of the cardiovascular system. He showed the importance of the nervous system in regulating the body's reactivity under stress, the role of the dominant in the development and prevention of the pathogenetic process. Formulated a position on previously unknown creative connections - intercellular molecular correlative interactions that contribute to the development and preservation of the structural and functional organization of a multicellular organism. Under the leadership of G.I. Kositsky developed a model of reversible myocardial ischemia, which made it possible to detect the influence of the reflexogenic zone of the heart on the functions of a number of internal organs. The issues of regulation of intercellular interactions in the myocardium, important for understanding the nature of the blockade of excitation in the heart, the development of arrhythmias, fibrillations and spontaneous defibrillation of the heart, were studied. An original idea of ​​the “cluster” structural and functional organization of the myocardium is formulated. He did a lot to improve the methods of teaching physiology in medicine. universities Joint with E.B. Babsky, A.A. Zubkov, B.I. Khodorov wrote the textbook “Human Physiology”, which went through its 12th edition. in our country and abroad. Author of original textbooks, including those on programmed training. Consisted before. Problem Commission on Physiology of the Medical Scientist. Council of the Ministry of Health of the RSFSR, member of the presidium of the All-Union Board. physiol. about-va them. I.P. Pavlova, deputy executive editor ed. Department "Physiology" 3rd ed. BME, member of the editorial boards of the journals “Advances of Physiological Sciences” and “Cardiology”, head of the Joint Section of Experimental Cardiology of Washing, Physiol., Pathophysiol. and cardiol. scientific society, member of the International Relations Commission of the Soviet Peace Committee. Awarded the Order of the Red Banner and medals.

-- [ Page 1 ] --

EDUCATIONAL LITERATURE

For medical students

Physiology

person

Edited by

member-corr. Academy of Medical Sciences of the USSR G. I. KOSITSKY

THIRD EDITION,

RECYCLED

AND EXTRA

Approved by the Main Directorate of Education

institutions of the Ministry of Health

protection of the USSR as a textbook

for medical students

Moscow “Medicine” 1985

E. B. BABSKY V. D. GLEBOVSKY, A. B. KOGAN, G. F. KOROTKO,

G. I. KOSITSKY, V. M. POKROVSKY, Y. V. NATOCHIN, V. P.

SKIPETROV, B. I. KHODOROV, A. I. SHAPOVALOV, I. ​​A. SHEVELEV Reviewer I. D. Boyenko, prof., head. Department of Normal Physiology, Voronezh Medical Institute named after. N. N. Burdenko Human Physiology / Ed. G.I. Kositsky. - F50 3rd ed., revised. and additional - M.: Medicine, 1985. 544 p., ill.

In the lane: 2 r. 20 k. 15 0 000 copies.

The third edition of the textbook (the second was published in 1972) was written in accordance with the achievements of modern science. New facts and concepts are presented, new chapters are included: “Features of higher nervous activity of a person”, “Elements of labor physiology, mechanisms of training and adaptation”, sections covering issues of biophysics and physiological cybernetics are expanded. Nine chapters of the textbook were written anew, the rest were largely revised.

The textbook corresponds to the program approved by the USSR Ministry of Health and is intended for students of medical institutes.

2007020000-241 BBK 28. 039(01) - Medicine Publishing House, PREFACE 12 years have passed since the previous edition of the textbook “Human Physiology”.

The responsible editor and one of the authors of the book, Academician of the Academy of Sciences of the Ukrainian SSR E.B. Babsky, according to whose manuals many generations of students studied physiology, have passed away.

Shapovalov and prof. Yu. V. Natochin (head of laboratories of the I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the USSR Academy of Sciences), prof. V.D. Glebovsky (Head of the Department of Physiology, Leningrad Pediatric Medical Institute), prof. A.B. Kogan (Head of the Department of Human and Animal Physiology and Director of the Institute of Neurocybernetics of Rostov State University), prof. G. F. Korotko (Head of the Department of Physiology, Andijan Medical Institute), prof. V.M. Pokrovsky (Head of the Department of Physiology, Kuban Medical Institute), prof. B.I. Khodorov (head of the laboratory of the A.V. Vishnevsky Institute of Surgery of the USSR Academy of Medical Sciences), prof. I. A. Shevelev (head of the laboratory of the Institute of Higher Nervous Activity and Neurophysiology of the USSR Academy of Sciences).

Over the past time, a large number of new facts, views, theories, discoveries and trends in our science have appeared. In this regard, 9 chapters in this edition had to be written anew, and the remaining 10 chapters had to be revised and supplemented. At the same time, to the extent possible, the authors tried to preserve the text of these chapters.

The new sequence of presentation of the material, as well as its combination into four main sections, is dictated by the desire to give the presentation logical harmony, consistency and, as far as possible, to avoid duplication of material.

The content of the textbook corresponds to the physiology program approved in the year. Critical comments about the project and the program itself, expressed in the resolution of the Bureau of the Department of Physiology of the USSR Academy of Sciences (1980) and at the All-Union Meeting of Heads of Physiology Departments of Medical Universities (Suzdal, 1982), were also taken into account. In accordance with the program, chapters were introduced into the textbook that were missing in the previous edition: “Features of higher nervous activity of man” and “Elements of labor physiology, mechanisms of training and adaptation,” and sections covering issues of particular biophysics and physiological cybernetics were expanded. The authors took into account that in 1983 a textbook of biophysics for students of medical institutes was published (ed.

prof. Yu.A.Vladimirov) and that the elements of biophysics and cybernetics are presented in the textbook by prof. A.N. Remizov “Medical and biological physics”.

Due to the limited volume of the textbook, it was necessary, unfortunately, to omit the chapter “History of Physiology”, as well as excursions into history in individual chapters. Chapter 1 gives only outlines of the formation and development of the main stages of our science and shows its importance for medicine.

Our colleagues provided great assistance in creating the textbook. At the All-Union Meeting in Suzdal (1982), the structure was discussed and approved, and valuable suggestions were made regarding the content of the textbook. Prof. V.P. Skipetrov revised the structure and edited the text of the 9th chapter and, in addition, wrote its sections relating to blood coagulation. Prof. V. S. Gurfinkel and R. S. Person wrote subsection 6 “Regulation of movements.” Assoc. N. M. Malyshenko presented some new materials for Chapter 8. Prof. I.D.Boenko and his staff expressed many useful comments and wishes as reviewers.

Employees of the Department of Physiology II MOLGMI named after N. I. Pirogova prof. L. A. Miyutin associate professors I. A. Murashova, S. A. Sevastopolskaya, T. E. Kuznetsova, candidate of medical sciences „" mpngush and L M Popova took part in the discussion of the manuscript of some chapters.

I would like to express our deep gratitude to all these comrades.

The authors are fully aware that in such a difficult task as creating a modern textbook, shortcomings are inevitable and therefore will be grateful to everyone who makes critical comments and suggestions about the textbook.

Corresponding member of the USSR Academy of Medical Sciences, prof. G. I. KOSIIDKY Chapter PHYSIOLOGY AND ITS SIGNIFICANCE Physiology (from the Greek physis - nature and logos - teaching) is the science of the life activity of the whole organism and its individual parts: cells, tissues, organs, functional systems. Physiology seeks to reveal the mechanisms of the functions of a living organism, their relationship with each other, regulation and adaptation to the external environment, origin and formation in the process of evolution and individual development of the individual.

Physiological patterns are based on data on the macro- and microscopic structure of organs and tissues, as well as on the biochemical and biophysical processes occurring in cells, organs and tissues. Physiology synthesizes specific information obtained by anatomy, histology, cytology, molecular biology, biochemistry, biophysics and other sciences, combining them into a single system of knowledge about the body.

Thus, physiology is a science that implements a systematic approach, i.e.

study of the body and all its elements as systems. The systems approach focuses the researcher primarily on revealing the integrity of the object and the mechanisms that support it, i.e. to identify diverse types of connections of a complex object and reduce them into a single theoretical picture.

The object of study of physiology is a living organism, the functioning of which as a whole is not the result of a simple mechanical interaction of its constituent parts. The integrity of the organism does not arise as a result of the influence of some supramaterial essence, which unquestioningly subjugates all the material structures of the organism. Similar interpretations of the integrity of the organism existed and still exist in the form of a limited mechanistic (metaphysical) or no less limited idealistic (vitalistic) approach to the study of life phenomena.

The errors inherent in both approaches can be overcome only by studying these problems from a dialectical-materialist position. Therefore, the patterns of activity of the organism as a whole can only be understood on the basis of a consistently scientific worldview. For its part, the study of physiological laws provides rich factual material illustrating a number of provisions of dialectical materialism. The connection between physiology and philosophy is thus two-way.

Physiology and medicine By revealing the basic mechanisms that ensure the existence of an entire organism and its interaction with the environment, physiology makes it possible to find out and study the causes, conditions and nature of disturbances in the activity of these mechanisms during illness. It helps to determine the ways and means of influencing the body, with the help of which its functions can be normalized, i.e. restore health.

Therefore, physiology is the theoretical basis of medicine; physiology and medicine are inseparable. The doctor assesses the severity of the disease by the degree of functional impairment, i.e. by the magnitude of deviation from the norm of a number of physiological functions. Currently, such deviations are measured and quantified. Functional (physiological) studies are the basis of clinical diagnosis, as well as a method for assessing the effectiveness of treatment and prognosis of diseases. Examining the patient, establishing the degree of impairment of physiological functions, the doctor sets himself the task of returning these functions to normal.

However, the importance of physiology for medicine is not limited to this. The study of the functions of various organs and systems has made it possible to simulate these functions using instruments, devices and devices created by human hands. In this way, an artificial kidney (hemodialysis machine) was constructed. Based on the study of the physiology of the heart rhythm, a device for electrical stimulation of the heart was created, which ensures normal cardiac activity and the possibility of returning to work for patients with severe heart damage. An artificial heart and artificial blood circulation devices (heart-lung machines) have been manufactured, which make it possible to turn off the patient’s heart during a complex heart operation. There are defibrillation devices that restore normal cardiac activity in case of fatal disorders of the contractile function of the heart muscle.

Research in the field of respiratory physiology made it possible to design a device for controlled artificial respiration (“iron lungs”). Devices have been created that can be used to turn off a patient’s breathing for a long time during operations or to maintain the life of the body for years in case of damage to the respiratory center. Knowledge of the physiological laws of gas exchange and gas transport helped to create installations for hyperbaric oxygenation. It is used for fatal lesions of the blood system, as well as the respiratory and cardiovascular systems.

Based on the laws of brain physiology, techniques for a number of complex neurosurgical operations have been developed. Thus, electrodes are implanted into the cochlea of ​​a deaf person, through which electrical impulses are sent from artificial sound receivers, which restores hearing to a certain extent.

These are just a few examples of the use of the laws of physiology in the clinic, but the significance of our science goes far beyond the boundaries of just medical medicine.

The role of physiology in ensuring human life and activity in various conditions The study of physiology is necessary for scientific substantiation and creation of conditions for a healthy lifestyle that prevents diseases. Physiological laws are the basis for the scientific organization of labor in modern production. Physiology has made it possible to develop a scientific basis for various individual training regimes and sports loads that underlie modern sports achievements. And not only sports. If you need to send a person into space or lower him into the depths of the ocean, undertake an expedition to the north and south poles, reach the peaks of the Himalayas, explore the tundra, taiga, desert, place a person in conditions of extremely high or low temperatures, move him to different time zones or climates technical conditions, then physiology helps to justify and provide everything necessary for human life and work in such extreme conditions.

Physiology and technology Knowledge of the laws of physiology was required not only for scientific organization and increasing labor productivity. Over billions of years of evolution, nature is known to have achieved the highest perfection in the design and control of the functions of living organisms. The use in technology of principles, methods and methods operating in the body opens up new prospects for technical progress. Therefore, at the intersection of physiology and technical sciences, a new science—bionics—was born.

The successes of physiology contributed to the creation of a number of other fields of science.

V. HARVEY (1578--1657) DEVELOPMENT OF METHODS OF PHYSIOLOGICAL RESEARCH Physiology was born as an experimental science. She obtains all data through direct research into the vital processes of animal and human organisms. The founder of experimental physiology was the famous English physician William Harvey.

“Three hundred years ago, amid the deep darkness and now difficult to imagine confusion that reigned in ideas about the activities of animal and human organisms, but illuminated by the inviolable authority of the scientific classical heritage, the physician William Harvey spied one of the most important functions of the body - blood circulation, and thereby laid the foundation a new department of precise human knowledge of animal physiology,” wrote I.P. Pavlov. However, for two centuries after the discovery of blood circulation by Harvey, the development of physiology occurred slowly. It is possible to list relatively few fundamental works of the 17th-18th centuries. This is the opening of capillaries (Malpighi), the formulation of the principle of reflex activity of the nervous system (Descartes), the measurement of blood pressure (Hels), the formulation of the law of conservation of matter (M.V. Lomonosov), the discovery of oxygen (Priestley) and the commonality of combustion and gas exchange processes ( Lavoisier), the discovery of “animal electricity”, i.e.

the ability of living tissues to generate electrical potentials (Galvani), and some other works.

Observation as a method of physiological research. The comparatively slow development of experimental physiology over the two centuries after Harvey's work is explained by the low level of production and development of natural science, as well as the difficulties of studying physiological phenomena through their usual observation. Such a methodological technique was and remains the cause of numerous errors, since the experimenter must conduct experiments, see and remember many complex processes and phenomena, which is a difficult task . The difficulties created by the method of simple observation of physiological phenomena are eloquently evidenced by the words of Harvey: “The speed of cardiac motion does not make it possible to distinguish how systole and diastole occur, and therefore it is impossible to know at what moment and in which part expansion and contraction occur. Indeed, I could not distinguish systole from diastole, since in many animals the heart appears and disappears in the blink of an eye, with the speed of lightning, so it seemed to me that once there was systole and here there was diastole, and another time it was the other way around. There is difference and confusion in everything.”

Indeed, physiological processes are dynamic phenomena. They are constantly developing and changing. Therefore, it is possible to directly observe only 1-2 or, at best, 2-3 processes. However, in order to analyze them, it is necessary to establish the relationship of these phenomena with other processes that remain unnoticed with this method of research. In this regard, simple observation of physiological processes as a research method is a source of subjective errors. Usually observation allows us to establish only the qualitative side of phenomena and makes it impossible to study them quantitatively.

An important milestone in the development of experimental physiology was the invention of the kymograph and the introduction of a method of graphically recording blood pressure by the German scientist Karl Ludwig in 1843.

Graphic registration of physiological processes. The graphical recording method marked a new stage in physiology. It made it possible to obtain an objective record of the process being studied, which minimized the possibility of subjective errors. In this case, the experiment and analysis of the phenomenon under study could be carried out in two stages.

During the experiment itself, the experimenter's task was to obtain high-quality recordings - curves. The analysis of the obtained data could be carried out later, when the experimenter’s attention was no longer distracted by the experiment.

The graphic recording method made it possible to record simultaneously (synchronously) not one, but several (theoretically unlimited number) physiological processes.

Quite soon after the invention of blood pressure recording, methods for recording the contraction of the heart and muscles were proposed (Engelman), an air transmission method was introduced (Marey’s capsule), which made it possible to record, sometimes at a considerable distance from the object, a number of physiological processes in the body: respiratory movements of the chest and abdominal cavity, peristalsis and changes in the tone of the stomach, intestines, etc. A method was proposed for recording vascular tone (Mosso plethysmography), changes in volume, various internal organs - oncometry, etc.

Research of bioelectric phenomena. An extremely important direction in the development of physiology was marked by the discovery of “animal electricity”. The classic “second experiment” of Luigi Galvani showed that living tissues are a source of electrical potentials capable of influencing the nerves and muscles of another organism and causing muscle contraction. Since then, for almost a century, the only indicator of potentials generated by living tissues (bioelectric potentials) was a frog neuromuscular preparation. He helped discover the potentials generated by the heart during its activity (the experience of Kölliker and Müller), as well as the need for continuous generation of electrical potentials for constant muscle contraction (the experience of “secondary tetanus” by Mateuci). It became clear that bioelectric potentials are not random (side) phenomena in the activity of living tissues, but signals with the help of which commands are transmitted in the body to the nervous system and from it to muscles and other organs, and thus living tissues interact with each other , using "electric language".

It was possible to understand this “language” much later, after the invention of physical devices that captured bioelectric potentials. One of the first such devices was a simple telephone. The remarkable Russian physiologist N.E. Vvedensky, using a telephone, discovered a number of the most important physiological properties of nerves and muscles. Using the phone, we were able to listen to bioelectric potentials, i.e. explore them through observation. A significant step forward was the invention of a technique for objective graphic recording of bioelectric phenomena. The Dutch physiologist Einthoven invented a string galvanometer - a device that made it possible to register on photo paper the electrical potentials arising during the activity of the heart - an electrocardiogram (ECG). In our country, the pioneer of this method was the largest physiologist, student of I.M. Sechenov and I.P. Pavlov, A.F. Samoilov, who worked for some time in the Einthoven laboratory in Leiden.

History has preserved interesting documents. A. F. Samoilov wrote a humorous letter in 1928:

“Dear Einthoven, I am writing a letter not to you, but to your dear and respected string galvanometer. That’s why I turn to him: Dear galvanometer, I just learned about your anniversary.

25 years ago you drew the first electrocardiogram. Congratulations. I don’t want to hide from you that I like you, despite the fact that you sometimes play pranks. I am amazed at how much you have achieved in 25 years. If we could count the number of meters and kilometers of photographic paper used to record your strings in all parts of the world, the resulting numbers would be enormous. You have created a new industry. You also have philological merits;

Very soon the author received a response from Einthoven, who wrote: “I exactly fulfilled your request and read the letter to the galvanometer. Undoubtedly, he listened and accepted with pleasure and joy everything that you wrote. He had no idea that he had done so much for humanity. But at the point where you say that he cannot read, he suddenly became furious... so much so that my family and I even became agitated. He shouted: What, I can’t read? This is a terrible lie. Am I not reading all the secrets of the heart? “Indeed, electrocardiography very soon moved from physiological laboratories to the clinic as a very advanced method for studying the condition of the heart, and many millions of patients today owe their lives to this method.

Samoilov A.F. Selected articles and speeches.-M.-L.: Publishing House of the USSR Academy of Sciences, 1946, p. 153.

Subsequently, the use of electronic amplifiers made it possible to create compact electrocardiographs, and telemetry methods make it possible to record ECGs from astronauts in orbit, from athletes on the track, and from patients in remote areas, from where the ECG is transmitted via telephone wires to large cardiological institutions for comprehensive analysis.

Objective graphic recording of bioelectric potentials served as the basis for the most important branch of our science - electrophysiology. A major step forward was the proposal of the English physiologist Adrian to use electronic amplifiers to record bioelectric phenomena. Soviet scientist V.V. Pravdich Neminsky was the first to register the biocurrents of the brain - he obtained an electroencephalogram (EEG). This method was later improved by the German scientist Berger. Currently, electroencephalography is widely used in the clinic, as well as graphic recording of electrical potentials of muscles (electromyography), nerves and other excitable tissues and organs. This made it possible to conduct a subtle assessment of the functional state of these organs and systems. For physiology itself, these methods were also of great importance: they made it possible to decipher the functional and structural mechanisms of the activity of the nervous system and other organs and tissues, and the mechanisms of regulation of physiological processes.

An important milestone in the development of electrophysiology was the invention of microelectrodes, i.e. the thinnest electrodes, the tip diameter of which is equal to fractions of a micron. These electrodes, with the help of appropriate devices - micromanipulators, can be introduced directly into the cell and bioelectric potentials can be recorded intracellularly.

Microelectrodes made it possible to decipher the mechanisms of generation of biopotentials, i.e. processes occurring in cell membranes. Membranes are the most important formations, since through them the processes of interaction of cells in the body and individual elements of the cell with each other are carried out. The science of the functions of biological membranes—membranology—has become an important branch of physiology.

Methods of electrical stimulation of organs and tissues. A significant milestone in the development of physiology was the introduction of the method of electrical stimulation of organs and tissues.

Living organs and tissues are capable of responding to any influence: thermal, mechanical, chemical, etc.; electrical stimulation, by its nature, is closest to the “natural language” with the help of which living systems exchange information. The founder of this method was the German physiologist Dubois-Reymond, who proposed his famous “sleigh apparatus” (induction coil) for dosed electrical stimulation of living tissues.

Currently, electronic stimulators are used for this, allowing one to receive electrical impulses of any shape, frequency and strength. Electrical stimulation has become an important method for studying the functions of organs and tissues. This method is widely used in the clinic. Designs of various electronic stimulators have been developed that can be implanted into the body. Electrical stimulation of the heart has become a reliable way to restore the normal rhythm and functions of this vital organ and has returned hundreds of thousands of people to work. Electrical stimulation of skeletal muscles has been successfully used, and methods of electrical stimulation of brain areas using implanted electrodes are being developed. The latter, using special stereotactic devices, are introduced into strictly defined nerve centers (with an accuracy of fractions of a millimeter). This method, transferred from physiology to the clinic, made it possible to cure thousands of severe neurological patients and obtain a large amount of important data on the mechanisms of the human brain (N. P. Bekhtereva). We have talked about this not only to give an idea of ​​some of the methods of physiological research, but also to illustrate the importance of physiology for the clinic.

In addition to recording electrical potentials, temperature, pressure, mechanical movements and other physical processes, as well as the results of the impact of these processes on the body, chemical methods are widely used in physiology.

Chemical methods in physiology. The language of electrical signals is not the most universal in the body. The most common is the chemical interaction of vital processes (chains of chemical processes occurring in living tissues). Therefore, a field of chemistry arose that studies these processes - physiological chemistry. Today it has turned into an independent science - biological chemistry, the data of which reveal the molecular mechanisms of physiological processes. A physiologist in his experiments widely uses chemical methods, as well as methods that arose at the intersection of chemistry, physics and biology. These methods have given rise to new branches of science, for example, biophysics, which studies the physical side of physiological phenomena.

The physiologist widely uses the method of labeled atoms. In modern physiological research, other methods borrowed from the exact sciences are also used. They provide truly invaluable information when analyzing certain mechanisms of physiological processes.

Electrical recording of non-electrical quantities. Significant progress in physiology today is associated with the use of radio-electronic technology. Sensors are used - converters of various non-electrical phenomena and quantities (motion, pressure, temperature, concentration of various substances, ions, etc.) into electrical potentials, which are then amplified by electronic amplifiers and recorded by oscilloscopes. A huge number of different types of such recording devices have been developed, which make it possible to record many physiological processes on an oscilloscope. A number of devices use additional effects on the body (ultrasonic or electromagnetic waves, high-frequency electrical vibrations, etc.). In such cases, the change in the magnitude of the parameters of these effects that change certain physiological functions is recorded. The advantage of such devices is that the transducer-sensor can be mounted not on the organ being studied, but on the surface of the body. Waves, vibrations, etc. affecting the body. penetrate the body and, after affecting the function or organ under study, are recorded by a sensor. This principle is used, for example, to build ultrasonic flow meters that determine the speed of blood flow in vessels, rheographs and rheoplethysmographs that record changes in the amount of blood in various parts of the body, and many other devices. Their advantage is the ability to study the body at any time without preliminary operations. In addition, such studies do not harm the body. Most modern methods of physiological research in the clinic are based on these principles. In the USSR, the initiator of the use of radioelectronic technology for physiological research was Academician V.V. Parin.

A significant advantage of such recording methods is that the physiological process is converted by the sensor into electrical oscillations, and the latter can be amplified and transmitted via wires or radio to any distance from the object under study. This is how telemetry methods arose, with the help of which it is possible in a ground laboratory to record physiological processes in the body of an astronaut in orbit, a pilot in flight, an athlete on the track, a worker during work, etc. The registration itself does not in any way interfere with the activities of the subjects.

However, the deeper the analysis of processes, the greater the need for synthesis arises, i.e. creating a whole picture of phenomena from individual elements.

The task of physiology is to, along with deepening the analysis, continuously carry out synthesis, to give a holistic picture of the body as a system.

The laws of physiology make it possible to understand the reaction of the body (as an integral system) and all its subsystems under certain conditions, under certain influences, etc.

Therefore, any method of influencing the body, before entering clinical practice, undergoes comprehensive testing in physiological experiments.

Acute experimental method. The progress of science is associated not only with the development of experimental techniques and research methods. It greatly depends on the evolution of the thinking of physiologists, on the development of methodological and methodological approaches to the study of physiological phenomena. From the beginning until the 80s of the last century, physiology remained an analytical science. She divided the body into separate organs and systems and studied their activity in isolation. The main methodological technique of analytical physiology was experiments on isolated organs, or so-called acute experiments. Moreover, in order to gain access to any internal organ or system, the physiologist had to engage in vivisection (live section).

The animal was tied to a machine and a complex and painful operation was performed.

It was hard work, but science did not know any other way to penetrate deep into the body.

It was not only the moral side of the problem. Cruel torture and unbearable suffering to which the body was subjected grossly disrupted the normal course of physiological phenomena and did not make it possible to understand the essence of processes that occur normally under natural conditions. The use of anesthesia and other methods of pain relief did not help significantly. Fixation of the animal, exposure to narcotic substances, surgery, blood loss - all this completely changed and disrupted the normal course of life activities. A vicious circle has formed. In order to study a particular process or function of an internal organ or system, it was necessary to penetrate into the depths of the organism, and the very attempt of such penetration disrupted the flow of vital processes, for the study of which the experiment was undertaken. In addition, the study of isolated organs did not provide an idea of ​​their true function in the conditions of a complete, undamaged organism.

Chronic experiment method. The greatest merit of Russian science in the history of physiology was that one of its most talented and bright representatives I.P.

Pavlov managed to find a way out of this impasse. I. P. Pavlov was very painful about the shortcomings of analytical physiology and acute experimentation. He found a way to look deep into the body without violating its integrity. This was a method of chronic experimentation carried out on the basis of “physiological surgery.”

On an anesthetized animal, under sterile conditions and in compliance with the rules of surgical technique, a complex operation was previously carried out, allowing access to one or another internal organ, a “window” was made into the hollow organ, a fistula tube was implanted, or the gland duct was brought out and sutured to the skin. The experiment itself began many days later, when the wound healed, the animal recovered and, in terms of the nature of the physiological processes, was practically no different from a normal healthy one. Thanks to the applied fistula, it was possible to study for a long time the course of certain physiological processes under natural behavioral conditions.

PHYSIOLOGY OF AN INTEGRAL ORGANISM It is well known that science develops depending on the success of methods.

Pavlov's method of chronic experiment created a fundamentally new science - physiology of the whole organism, synthetic physiology, which was able to identify the influence of the external environment on physiological processes, detect changes in the functions of various organs and systems to ensure the life of the organism in various conditions.

With the advent of modern technical means for studying vital processes, it has become possible to study the functions of many internal organs, not only in animals, but also in humans, without preliminary surgical operations. “Physiological surgery” as a methodological technique in a number of branches of physiology has been supplanted by modern methods of bloodless experimentation. But the point is not in this or that specific technical technique, but in the methodology of physiological thinking. I.P. Pavlov created a new methodology, and physiology developed as a synthetic science and a systematic approach became organically inherent in it.

A complete organism is inextricably linked with the external environment surrounding it, and therefore, as I.M. Sechenov wrote, the scientific definition of an organism should also include the environment that influences it. The physiology of the whole organism studies not only the internal mechanisms of self-regulation of physiological processes, but also the mechanisms that ensure continuous interaction and inextricable unity of the organism with the environment.

Regulation of vital processes, as well as the interaction of the body with the environment, is carried out on the basis of principles common to regulation processes in machines and automated production. These principles and laws are studied by a special field of science - cybernetics.

Physiology and cybernetics I. P. PAVLOV (1849-1936) Cybernetics (from the Greek kybernetike - the art of control) - the science of controlling automated processes. Control processes, as is known, are carried out by signals carrying certain information. In the body, such signals are nerve impulses of an electrical nature, as well as various chemical substances.

Cybernetics studies the processes of perception, encoding, processing, storage and reproduction of information. In the body, there are special devices and systems for these purposes (receptors, nerve fibers, nerve cells, etc.).

Technical cybernetic devices have made it possible to create models that reproduce some functions of the nervous system. However, the functioning of the brain as a whole is not yet amenable to such modeling, and further research is needed.

The union of cybernetics and physiology arose only three decades ago, but during this time the mathematical and technical arsenal of modern cybernetics has provided significant advances in the study and modeling of physiological processes.

Mathematics and computer technology in physiology. Simultaneous (synchronous) registration of physiological processes allows for their quantitative analysis and study of the interaction between various phenomena. This requires precise mathematical methods, the use of which also marked a new important stage in the development of physiology. Mathematization of research allows the use of electronic computers in physiology. This not only increases the speed of information processing, but also makes it possible to carry out such processing directly at the time of the experiment, which allows you to change its course and the tasks of the study itself in accordance with the results obtained.

Thus, the spiral in the development of physiology seemed to have ended. At the dawn of this science, research, analysis and evaluation of the results were carried out by the experimenter simultaneously in the process of observation, directly during the experiment itself. Graphic registration made it possible to separate these processes in time and process and analyze the results after the end of the experiment.

Radio electronics and cybernetics have made it possible to reconnect the analysis and processing of results with the conduct of the experiment itself, but on a fundamentally different basis: the interaction of many different physiological processes is simultaneously studied and the results of such interaction are analyzed quantitatively. This made it possible to conduct a so-called controlled automatic experiment, in which a computer helps the researcher not only analyze the results, but also change the course of the experiment and the formulation of tasks, as well as the types of influence on the body, depending on the nature of the body’s reactions that arise directly during experience. Physics, mathematics, cybernetics and other exact sciences have re-equipped physiology and provided the doctor with a powerful arsenal of modern technical means for accurately assessing the functional state of the body and for influencing the body.

Mathematical modeling in physiology. Knowledge of physiological patterns and quantitative relationships between various physiological processes made it possible to create their mathematical models. With the help of such models, these processes are reproduced on electronic computers, exploring various reaction options, i.e. their possible future changes under certain influences on the body (medicines, physical factors or extreme environmental conditions). Already now, the union of physiology and cybernetics has proven useful during heavy surgical operations and in other emergency conditions that require an accurate assessment of both the current state of the most important physiological processes of the body and the anticipation of possible changes. This approach allows us to significantly increase the reliability of the “human factor” in difficult and critical parts of modern production.

Physiology of the 20th century. has made significant progress not only in the field of revealing the mechanisms of life processes and controlling these processes. She made a breakthrough into the most complex and mysterious area - into the area of ​​psychic phenomena.

The physiological basis of the psyche - the higher nervous activity of humans and animals - has become one of the important objects of physiological research.

OBJECTIVE STUDY OF HIGHER NERVOUS ACTIVITY For thousands of years, it was generally accepted that human behavior is determined by the influence of a certain immaterial entity (“soul”), which the physiologist is not able to know.

I.M. Sechenov was the first physiologist in the world who dared to imagine behavior based on the principle of reflex, i.e. based on the mechanisms of nervous activity known in physiology. In his famous book “Reflexes of the Brain,” he showed that no matter how complex the external manifestations of human mental activity may seem to us, they sooner or later come down to only one thing - muscle movement.

“Whether a child smiles at the sight of a new toy, whether Garibaldi laughs when he is persecuted for excessive love for his homeland, whether Newton invents world laws and writes them on paper, whether a girl trembles at the thought of a first date, the end result of the thought is always one thing - muscular movement,” wrote I.M. Sechenov.

Analyzing the formation of a child’s thinking, I.M. Sechenov showed step by step that this thinking is formed as a result of influences from the external environment, combined with each other in various combinations, causing the formation of different associations.

Our thinking (spiritual life) is naturally formed under the influence of environmental conditions, and the brain is an organ that accumulates and reflects these influences. No matter how complex the manifestations of our mental life may seem to us, our internal psychological makeup is a natural result of the conditions of upbringing and environmental influences. 999/1000 of a person’s mental content depends on the conditions of upbringing, environmental influences in the broad sense of the word, wrote I.M. Sechenov, and only 1/1000 of it is determined by congenital factors. Thus, the principle of determinism, the basic principle of the materialistic worldview, was first extended to the most complex area of ​​life phenomena, to the processes of human spiritual life. I.M. Sechenov wrote that someday a physiologist will learn to analyze external manifestations of brain activity as accurately as a physicist can analyze a musical chord. I.M. Sechenov’s book was a work of genius, affirming materialist positions in the most complex areas of human spiritual life.

Sechenov's attempt to substantiate the mechanisms of brain activity was a purely theoretical attempt. The next step was necessary - experimental studies of the physiological mechanisms underlying mental activity and behavioral reactions. And this step was taken by I.P. Pavlov.

The fact that it was I.P. Pavlov, and not anyone else, who became the heir to I.M. Sechenov’s ideas and was the first to penetrate the basic secrets of the work of the higher parts of the brain is not accidental. The logic of his experimental physiological studies led to this. Studying vital processes in the body under conditions of natural animal behavior, I.

P. Pavlov drew attention to the important role of mental factors influencing all physiological processes. The observation of I. P. Pavlov did not escape the fact that saliva, I. M. SECHENOV (1829-1905) gastric juice and other digestive juices begin to be secreted in the animal not only at the moment of eating, but long before eating, at the sight of food , the sound of the footsteps of the attendant who usually feeds the animal. I.P. Pavlov drew attention to the fact that appetite, the passionate desire for food, is as powerful a juice-secreting agent as food itself. Appetite, desire, mood, experiences, feelings - all these were mental phenomena. They were not studied by physiologists before I.P. Pavlov. I.P. Pavlov saw that the physiologist has no right to ignore these phenomena, since they powerfully interfere with the course of physiological processes, changing their character. Therefore, the physiologist was obliged to study them. But how? Before I.P. Pavlov, these phenomena were considered by a science called zoopsychology.

Having turned to this science, I.P. Pavlov had to move away from the solid ground of physiological facts and enter the realm of fruitless and groundless guesses regarding the apparent mental state of animals. To explain human behavior, the methods used in psychology are legitimate, since a person can always report his feelings, moods, experiences, etc. Animal psychologists blindly transferred data obtained from examining humans to animals, and also talked about “feelings,” “moods,” “experiences,” “desires,” etc. in an animal, without being able to check whether this is true or not. For the first time in Pavlov's laboratories, as many opinions arose about the mechanisms of the same facts as there were observers who saw these facts. Each of them interpreted them in his own way, and there was no way to verify the correctness of any of the interpretations. I.P. Pavlov realized that such interpretations were meaningless and therefore took a decisive, truly revolutionary step. Without trying to guess about certain internal mental states of the animal, he began to study the animal’s behavior objectively, comparing certain effects on the body with the body’s responses. This objective method made it possible to identify the laws underlying the behavioral reactions of the body.

The method of objective study of behavioral reactions created a new science - the physiology of higher nervous activity with its precise knowledge of the processes occurring in the nervous system under certain influences of the external environment. This science has given a lot to understanding the essence of the mechanisms of human mental activity.

The physiology of higher nervous activity created by I.P. Pavlov became the natural scientific basis of psychology. It became the natural science basis of Lenin’s theory of reflection and is of utmost importance in philosophy, medicine, pedagogy and in all those sciences that one way or another face the need to study the inner (spiritual) world of man.

The importance of the physiology of higher nervous activity for medicine. Teachings of I.P.

Pavlov's theory of higher nervous activity is of great practical importance. It is known that a patient is cured not only by medicines, a scalpel or a procedure, but also by the doctor’s word, trust in him, and a passionate desire to get well. All these facts were known to Hippocrates and Avicenna. However, for thousands of years they were perceived as proof of the existence of a powerful, “God-given soul” that subjugates the “perishable body.” The teachings of I.P. Pavlov tore off the veil of mystery from these facts.

It became clear that the seemingly magical effect of talismans, a sorcerer or the spells of a shaman is nothing more than an example of the influence of the higher parts of the brain on internal organs and the regulation of all life processes. The nature of this influence is determined by the influence of environmental conditions on the body, the most important of which for humans are social conditions - in particular, the exchange of thoughts in human society through words. For the first time in the history of science, I.P. Pavlov showed that the power of words lies in the fact that words and speech represent a special system of signals, inherent only to humans, which naturally changes behavior and mental status. Paul's teaching expelled idealism from the last, seemingly impregnable refuge - the idea of ​​a God-given “soul.” It placed a powerful weapon in the hands of the doctor, giving him the opportunity to use words correctly, showing the most important role of moral influence on the patient for the success of treatment.

CONCLUSION I. P. Pavlov can rightfully be considered the founder of modern physiology of the whole organism. Other outstanding Soviet physiologists also made a major contribution to its development. A. A. Ukhtomsky created the doctrine of the dominant as the main principle of the activity of the central nervous system (CNS). L. A. Orbeli founded the evolution of L. L. ORBELI A. A. UKHTOMSKY (1882-1958) (1875-1942) P. K. ANOKHIN K. M. BYKOV (1898-1974) (1886-1959) tion physiology. He authored fundamental works on the adaptive trophic function of the sympathetic nervous system. K. M. Bykov revealed the presence of conditioned reflex regulation of the functions of internal organs, showing that autonomic functions are not autonomous, that they are subject to the influence of the higher parts of the central nervous system and can change under the influence of conditioned signals. For humans, the most important conditioned signal is the word. This signal is capable of changing the activity of internal organs, which is of utmost importance for medicine (psychotherapy, deontology, etc.).

L. S. STERN I. S. BERITASHVILI (1878-1968) (1885-1974) P. K. Anokhin developed the doctrine of the functional system - a universal scheme for the regulation of physiological processes and behavioral reactions of the body.

The eminent neurophysiologist I. S. Beritov (Beritashvili) created a number of original directions in the physiology of the neuromuscular and central nervous systems. L. S. Stern is the author of the doctrine of the blood-brain barrier and histohematic barriers - regulators of the immediate internal environment of organs and tissues. V.V. Parin made major discoveries in the field of regulation of the cardiovascular system (Larin reflex). He is the founder of space physiology and the initiator of the introduction of radio electronics, cybernetics, and mathematics methods into physiological research. E. A. Asratyan created a doctrine about the mechanisms of compensation for impaired functions. He is the author of a number of fundamental works developing the main provisions of the teachings of I. P. Pavlov. V. N. Chernigovsky developed the doctrine of interoreceptors.

Soviet physiologists had priority in PARIN (1903-1971), the creation of an artificial heart (A. A. Bryukhonenko), EEG recording (V. V. Pravdich-Neminsky), the creation of such important and new directions in science as space physiology, labor physiology, physiology of sports, the study of physiological mechanisms of adaptation, regulation and internal mechanisms for the implementation of many physiological functions. These and many other studies are of paramount importance for medicine.

Knowledge of vital processes occurring in various organs and tissues, mechanisms of regulation of vital phenomena, understanding of the essence of the physiological functions of the body and the processes that interact with the environment represent the fundamental theoretical basis on which the training of the future doctor is based.

Section I GENERAL PHYSIOLOGY INTRODUCTION Each of the hundred trillion cells of the human body is distinguished by an extremely complex structure, the ability to self-organize and multilateral interaction with other cells. The number of processes carried out by each cell and the amount of information processed in this process far exceeds what takes place today in any large industrial plant. Nevertheless, the cell is only one of the relatively elementary subsystems in the complex hierarchy of systems that form a living organism.

All these systems are highly ordered. The normal functional structure of any of them and the normal existence of each element of the system (including each cell) are possible thanks to the continuous exchange of information between the elements (and between cells).

The exchange of information occurs through direct (contact) interaction between cells, as a result of the transport of substances with tissue fluid, lymph and blood (humoral communication - from the Latin humor - liquid), as well as during the transfer of bioelectric potentials from cell to cell, which represents the most a fast way to transmit information in the body. Multicellular organisms have developed a special system that provides perception, transmission, storage, processing and reproduction of information encoded in electrical signals. This is the nervous system that has reached its highest development in humans. To understand the nature of bioelectrical phenomena, i.e., the signals by which the nervous system transmits information, it is necessary first of all to consider some aspects of the general physiology of the so-called excitable tissues, which include nervous, muscle and glandular tissue.

Chapter PHYSIOLOGY OF EXCITABLE TISSUE All living cells have irritability, that is, the ability, under the influence of certain factors of the external or internal environment, the so-called stimuli, to move from a state of physiological rest to a state of activity. However, the term “excitable cells” is used only in relation to nerve, muscle and secretory cells that are capable of generating specialized forms of electrical potential oscillations in response to the action of a stimulus.

The first data on the existence of bioelectric phenomena (“animal electricity”) were obtained in the third quarter of the 18th century. at. studying the nature of the electrical discharge caused by some fish during defense and attack. A long-term scientific dispute (1791 -1797) between the physiologist L. Galvani and the physicist A. Volta about the nature of “animal electricity” ended with two major discoveries: facts were established indicating the presence of electrical potentials in nervous and muscle tissues, and a new method was discovered obtaining electric current using dissimilar metals - a galvanic element (“voltaic column”) was created. However, the first direct measurements of potentials in living tissues became possible only after the invention of galvanometers. A systematic study of potentials in muscles and nerves in a state of rest and excitement was begun by Dubois-Reymond (1848). Further advances in the study of bioelectrical phenomena were closely related to the improvement of techniques for recording fast oscillations of electrical potential (string, loop and cathode oscilloscopes) and methods for their removal from single excitable cells. A qualitatively new stage in the study of electrical phenomena in living tissues - the 40-50s of our century. Using intracellular microelectrodes, it was possible to directly record the electrical potentials of cell membranes. Advances in electronics have made it possible to develop methods for studying ionic currents flowing through a membrane when the membrane potential changes or when biologically active compounds act on membrane receptors. In recent years, a method has been developed that makes it possible to record ion currents flowing through single ion channels.

The following main types of electrical responses of excitable cells are distinguished:

local response;

spreading action potential and accompanying trace potentials;

excitatory and inhibitory postsynaptic potentials;

generator potentials, etc. All these potential fluctuations are based on reversible changes in the permeability of the cell membrane for certain ions. In turn, the change in permeability is a consequence of the opening and closing of ion channels existing in the cell membrane under the influence of an active stimulus.

The energy used in the generation of electrical potentials is stored in a resting cell in the form of concentration gradients of Na+, Ca2+, K+, C1~ ions on both sides of the surface membrane. These gradients are created and maintained by the work of specialized molecular devices, so-called membrane ion pumps. The latter use for their work metabolic energy released during the enzymatic breakdown of the universal cellular energy donor - adenosine triphosphoric acid (ATP).

The study of electrical potentials accompanying the processes of excitation and inhibition in living tissues is important both for understanding the nature of these processes and for identifying the nature of disturbances in the activity of excitable cells in various types of pathology.

In modern clinics, methods for recording the electrical potentials of the heart (electrocardiography), brain (electroencephalography) and muscles (electromyography) have become especially widespread.

RESTING POTENTIAL The term “membrane potential” (resting potential) is commonly used to refer to the transmembrane potential difference;

existing between the cytoplasm and the external solution surrounding the cell. When a cell (fiber) is in a state of physiological rest, its internal potential is negative in relation to the external one, which is conventionally taken as zero. In different cells, the membrane potential varies from -50 to -90 mV.

To measure the resting potential and monitor its changes caused by one or another effect on the cell, the technique of intracellular microelectrodes is used (Fig. 1).

The microelectrode is a micropipette, that is, a thin capillary extended from a glass tube. The diameter of its tip is about 0.5 microns. The micropipet is filled with saline solution (usually 3 M K.S1), a metal electrode (chlorinated silver wire) is immersed in it and connected to an electrical measuring device - an oscilloscope equipped with a direct current amplifier.

The microelectrode is installed over the object under study, for example, skeletal muscle, and then, using a micromanipulator - a device equipped with micrometric screws, it is inserted into the cell. An electrode of normal size is immersed in a normal saline solution containing the tissue being examined.

As soon as the microelectrode pierces the surface membrane of the cell, the oscillograph beam immediately deviates from its original (zero) position, thereby revealing the existence of a potential difference between the surface and the contents of the cell. Further advancement of the microelectrode inside the protoplasm does not affect the position of the oscilloscope beam. This indicates that the potential is indeed localized on the cell membrane.

When a microelectrode is successfully inserted, the membrane tightly covers its tip and the cell retains the ability to function for several hours without showing signs of damage.

There are many factors that change the resting potential of cells: application of electric current, changes in the ionic composition of the medium, exposure to certain toxins, disruption of oxygen supply to tissue, etc. In all those cases when the internal potential decreases (becomes less negative), talk about membrane depolarization;

the opposite shift in potential (increasing the negative charge on the inner surface of the cell membrane) is called hyperpolarization.

THE NATURE OF THE RESTING POTENTIAL Back in 1896, V. Yu. Chagovets put forward a hypothesis about the ionic mechanism of electrical potentials in living cells and made an attempt to apply Arrhenius’s theory of electrolytic dissociation to explain them. In 1902, Yu. Bernstein developed the membrane-ion theory, which was modified and experimentally substantiated by Hodgkin, Huxley and Katz (1949-1952). Currently, the latter theory enjoys universal acceptance. According to this theory, the presence of electrical potentials in living cells is due to the inequality in the concentration of Na+, K+, Ca2+ and C1~ ions inside and outside the cell and the different permeability of the surface membrane to them.

From the data in table. Figure 1 shows that the contents of the nerve fiber are rich in K+ and organic anions (which practically do not penetrate the membrane) and poor in Na+ and C1~.

The concentration of K+ in the cytoplasm of nerve and muscle cells is 40-50 times higher than in the external solution, and if the resting membrane were permeable only to these ions, then the resting potential would correspond to the equilibrium potassium potential (Ek), calculated using the Nernst formula :

where R is the gas constant, F is the Faraday number, T is the absolute temperature, Ko is the concentration of free potassium ions in the external solution, Ki is their concentration in the cytoplasm. To understand how this potential arises, consider the following model experiment (Fig. 2).

Let us imagine a vessel separated by an artificial semipermeable membrane. The pore walls of this membrane are electronegatively charged, so they allow only cations to pass through and are impermeable to anions. A saline solution containing K+ ions is poured into both halves of the vessel, but their concentration in the right side of the vessel is higher than in the left. As a result of this concentration gradient, K+ ions begin to diffuse from the right half of the vessel to the left, bringing their positive charge there. This leads to the fact that non-penetrating anions begin to accumulate near the membrane in the right half of the vessel. With their negative charge, they will electrostatically hold K+ at the surface of the membrane in the left half of the vessel. As a result, the membrane is polarized, and a potential difference corresponding to the equilibrium potassium potential (k) is created between its two surfaces.

The assumption that in the resting state the membrane of nerve and muscle fibers is selectively permeable to K+ and that it is their diffusion that creates the resting potential was made by Bernstein back in 1902 and confirmed by Hodgkin et al. in 1962 in experiments on isolated giant squid axons. The cytoplasm (axoplasm) was carefully squeezed out of a fiber with a diameter of about 1 mm, and the collapsed membrane was filled with an artificial saline solution. When the concentration of K+ in the solution was close to the intracellular value, a potential difference was established between the inner and outer sides of the membrane, close to the value of the normal resting potential (-50 = 80 mV), and the fiber conducted impulses. As the intracellular K+ concentration decreased and the external K+ concentration increased, the membrane potential decreased or even changed its sign (the potential became positive if the K+ concentration in the external solution was higher than in the internal one).

Such experiments have shown that the concentrated K+ gradient is indeed the main factor determining the magnitude of the resting potential of the nerve fiber. However, the resting membrane is permeable not only to K+, but (albeit to a much lesser extent) also to Na+. The diffusion of these positively charged ions into the cell reduces the absolute value of the internal negative potential of the cell created by K+ diffusion. Therefore, the resting potential of the fibers (-50 - 70 mV) is less negative than the potassium equilibrium potential calculated using the Nernst formula.

C1~ ions in nerve fibers do not play a significant role in the genesis of the resting potential, since the permeability of the resting membrane to them is relatively small. In contrast, in skeletal muscle fibers the permeability of the resting membrane for chlorine ions is comparable to potassium, and therefore the diffusion of C1~ into the cell increases the value of the resting potential. Calculated chlorine equilibrium potential (Ecl) at the ratio Thus, the value of the cell's resting potential is determined by two main factors: a) the ratio of the concentrations of cations and anions penetrating through the resting surface membrane;

b) the ratio of membrane permeabilities for these ions.

To quantitatively describe this pattern, the Goldman-Hodgkin-Katz equation is usually used:

where Em is the resting potential, Pk, PNa, Pcl are the permeability of the membrane for K+, Na+ and C1~ ions, respectively;

Cl0- are the external concentrations of K+, Na+ and Cl- ions and Ki+ Nai+ and Cli- are their internal concentrations.

It was calculated that in an isolated squid giant axon at Em = -50 mV there is the following relationship between the ionic permeabilities of the resting membrane:

Рк:РNa:РCl = 1:0.04:0.45.

The equation explains many of the changes in the cell's resting potential observed experimentally and in natural conditions, for example, its persistent depolarization under the influence of certain toxins that cause an increase in sodium permeability of the membrane. These toxins include plant poisons: veratridine, aconitine and one of the most powerful neurotoxins - batra hotoxin, produced by the skin glands of Colombian frogs.

Membrane depolarization, as follows from the equation, can also occur with unchanged PNA if the external concentration of K+ ions is increased (i.e., the Ko/Ki ratio is increased). This change in resting potential is by no means just a laboratory phenomenon. The fact is that the concentration of K+ in the intercellular fluid increases noticeably during the activation of nerve and muscle cells, accompanied by an increase in Pk. The concentration of K+ in the intercellular fluid increases especially significantly during disturbances of the blood supply (ischemia) to tissues, for example, myocardial ischemia. The resulting depolarization of the membrane leads to the cessation of the generation of action potentials, i.e., disruption of the normal electrical activity of cells.

THE ROLE OF METABOLISM IN THE GENESIS AND MAINTENANCE OF RESTING POTENTIAL (SODIUM PUMP OF MEMBRANES) Despite the fact that the fluxes of Na+ and K+ through the membrane at rest are small, the difference in the concentrations of these ions inside and outside the cell should eventually equalize if If there were no special molecular device in the cell membrane - a “sodium pump”, which ensures the removal (“pumping out”) of Na+ penetrating into it from the cytoplasm and the introduction (“pumping”) of K+ into the cytoplasm. The sodium pump moves Na+ and K+ against their concentration gradients, i.e. it does a certain amount of work. The direct source of energy for this work is an energy-rich (macroergic) compound - adenosine triphosphoric acid (ATP), which is a universal source of energy for living cells. The breakdown of ATP is carried out by protein macromolecules - the enzyme adenosine triphosphatase (ATPase), localized in the surface membrane of the cell. The energy released during the breakdown of one ATP molecule ensures the removal of three Na + ions from the cell in exchange for two K + ions entering the cell from the outside.

Inhibition of ATPase activity caused by certain chemical compounds (for example, the cardiac glycoside ouabain) disrupts the pump, causing the cell to lose K+ and become enriched in Na+. The same result is achieved by inhibition of oxidative and glycolytic processes in the cell, which ensure the synthesis of ATP. In experiments, this is achieved with the help of poisons that inhibit these processes. In conditions of impaired blood supply to tissues, weakening of the process of tissue respiration, the operation of the electrogenic pump is inhibited and, as a consequence, the accumulation of K+ in the intercellular gaps and depolarization of the membrane.

The role of ATP in the mechanism of active Na+ transport was directly proven in experiments on giant squid nerve fibers. It was found that by introducing ATP into the fiber, it was possible to temporarily restore the functioning of the sodium pump, impaired by the respiratory enzyme inhibitor cyanide.

Initially, it was believed that the sodium pump was electrically neutral, i.e., the number of exchanged Na+ and K+ ions was equal. It was later discovered that for every three Na+ ions removed from the cell, only two K+ ions enter the cell. This means that the pump is electrogenic: it creates a potential difference on the membrane that adds up to the resting potential.

This contribution of the sodium pump to the normal value of the resting potential is not the same in different cells: it is apparently insignificant in squid nerve fibers, but is significant for the resting potential (about 25% of the total value) in giant mollusk neurons and smooth muscles.

Thus, in the formation of the resting potential, the sodium pump plays a dual role: 1) creates and maintains a transmembrane concentration gradient of Na+ and K+;

2) generates a potential difference that is summed with the potential created by the diffusion of K+ along the concentration gradient.

ACTION POTENTIAL Action potential is a rapid fluctuation in membrane potential that occurs when nerve, muscle, and some other cells are excited. It is based on changes in the ionic permeability of the membrane. The amplitude and nature of temporary changes in the action potential depend little on the strength of the stimulus that causes it; it is only important that this strength is not less than a certain critical value, which is called the threshold of irritation. Having arisen at the site of irritation, the action potential spreads along the nerve or muscle fiber without changing its amplitude.

The presence of a threshold and the independence of the amplitude of the action potential from the strength of the stimulus that caused it are called the “all or nothing” law.

Under natural conditions, action potentials are generated in nerve fibers when receptors are stimulated or nerve cells are excited. The propagation of action potentials along nerve fibers ensures the transmission of information in the nervous system. Having reached the nerve endings, action potentials cause the secretion of chemicals (transmitters) that provide signal transmission to muscle or nerve cells. In muscle cells, action potentials initiate a chain of processes that cause a contractile act. Ions penetrating into the cytoplasm during the generation of action potentials have a regulatory effect on cell metabolism and, in particular, on the processes of synthesis of proteins that make up ion channels and ion pumps.

To record action potentials, extra- or intracellular electrodes are used. In extracellular abduction, the electrodes are brought to the outer surface of the fiber (cell). This makes it possible to discover that the surface of the excited area for a very short time (in a nerve fiber for a thousandth of a second) becomes negatively charged relative to the neighboring resting area.

The use of intracellular microelectrodes allows quantitative characterization of changes in membrane potential during the ascending and descending phases of the action potential. It has been established that during the ascending phase (depolarization phase), not only does the resting potential disappear (as was originally assumed), but a potential difference of the opposite sign occurs: the internal contents of the cell become positively charged in relation to the external environment, in other words, a reversion occurs membrane potential. During the descending phase (repolarization phase), the membrane potential returns to its original value. In Fig. Figures 3 and 4 show examples of recordings of action potentials in frog skeletal muscle fiber and squid giant axon. It can be seen that at the moment of reaching the apex (peak), the membrane potential is + 30 / + 40 mV and the peak oscillation is accompanied by long-term trace changes in the membrane potential, after which the membrane potential is established at the initial level. The duration of the action potential peak in various nerve and skeletal muscle fibers varies Fig. 5. Summation of trace potentials in the phrenic nerve of a cat during short-term stimulation with rhythmic impulses.

The rising portion of the action potential is not visible. Recordings begin with negative trace potentials (a), turning into positive potentials (b). The upper curve is the response to a single stimulus. With increasing stimulation frequency (from 10 to 250 per 1 s), the trace positive potential (trace hyperpolarization) increases sharply.

ranges from 0.5 to 3 ms, and the repolarization phase is longer than the depolarization phase.

The duration of the action potential, especially the repolarization phase, is closely dependent on temperature: when cooled by 10 °C, the duration of the peak increases approximately 3 times.

The changes in membrane potential following the peak of the action potential are called trace potentials.

There are two types of trace potentials - trace depolarization and trace hyperpolarization. The amplitude of trace potentials usually does not exceed several millivolts (5-10% of the peak height), and their duration in different fibers ranges from several milliseconds to tens and hundreds of seconds.

The dependence of the peak of the action potential and the trace depolarization can be considered using the example of the electrical response of a skeletal muscle fiber. From the entry shown in Fig. 3, it is clear that the descending phase of the action potential (repolarization phase) is divided into two unequal parts. At first, the potential drop occurs quickly, and then slows down significantly. This slow component of the descending phase of the action potential is called trail depolarization.

An example of the trace membrane hyperpolarization accompanying the peak of an action potential in a single (isolated) squid giant nerve fiber is shown in Fig. 4. In this case, the descending phase of the action potential directly passes into the phase of trace hyperpolarization, the amplitude of which in this case reaches 15 mV. Trace hyperpolarization is characteristic of many non-pulp nerve fibers of cold-blooded and warm-blooded animals. In myelinated nerve fibers, trace potentials are more complex. A trace depolarization can turn into a trace hyperpolarization, then sometimes a new depolarization occurs, only after which the resting potential is completely restored. Trace potentials, to a much greater extent than peaks of action potentials, are sensitive to changes in the initial resting potential, ionic composition of the medium, oxygen supply to the fiber, etc.

A characteristic feature of trace potentials is their ability to change during the process of rhythmic impulses (Fig. 5).

IONIC MECHANISM OF ACTION POTENTIAL APPEARANCE The action potential is based on changes in the ionic permeability of the cell membrane that consistently develop over time.

As noted, at rest the permeability of the membrane to potassium exceeds its permeability to sodium. As a result, the flow of K+ from the cytoplasm into the external solution exceeds the oppositely directed flow of Na+. Therefore, the outer side of the membrane at rest has a positive potential relative to the inner one.

When a cell is exposed to an irritant, the permeability of the membrane to Na+ increases sharply and ultimately becomes approximately 20 times greater than the permeability to K+. Therefore, the flow of Na+ from the external solution into the cytoplasm begins to exceed the outward potassium current. This leads to a change in the sign (reversion) of the membrane potential: the internal contents of the cell become positively charged relative to its outer surface. This change in membrane potential corresponds to the ascending phase of the action potential (depolarization phase).

The increase in membrane permeability to Na+ lasts only for a very short time. Following this, the permeability of the membrane for Na+ decreases again, and for K+ it increases.

The process leading to the decline earlier Fig. 6. The time course of changes in sodium (g) Na increased sodium permeability and potassium (gk) permeability of the giant membrane membrane is called sodium inactivation. squid axon during poten generation As a result of inactivation, Na+ flows into the action cial (V).

cytoplasm is sharply weakened. An increase in potassium permeability causes an increase in the flow of K+ from the cytoplasm into the external solution. As a result of these two processes, membrane repolarization occurs: the internal contents of the cell again acquire a negative charge in relation to the external solution. This change in potential corresponds to the descending phase of the action potential (repolarization phase).

One of the important arguments in favor of the sodium theory of the origin of action potentials was the fact that its amplitude was closely dependent on the concentration of Na+ in the external solution.

Experiments on giant nerve fibers perfused from the inside with saline solutions provided direct confirmation of the correctness of the sodium theory. It has been established that when the axoplasm is replaced with a saline solution rich in K+, the fiber membrane not only maintains the normal resting potential, but for a long time retains the ability to generate hundreds of thousands of action potentials of normal amplitude. If K+ in the intracellular solution is partially replaced by Na+ and thereby reduces the Na+ concentration gradient between the external environment and the internal solution, the amplitude of the action potential sharply decreases. When K+ is completely replaced by Na+, the fiber loses its ability to generate action potentials.

These experiments leave no doubt that the surface membrane is indeed the site of potential occurrence both at rest and during excitation. It becomes obvious that the difference in concentrations of Na+ and K+ inside and outside the fiber is the source of the electromotive force that causes the occurrence of the resting potential and the action potential.

In Fig. Figure 6 shows changes in membrane sodium and potassium permeability during action potential generation in the squid giant axon. Similar relationships occur in other nerve fibers, nerve cell bodies, as well as in skeletal muscle fibers of vertebrate animals. In the skeletal muscles of crustaceans and smooth muscles of vertebrates, Ca2+ ions play a leading role in the genesis of the ascending phase of the action potential. In myocardial cells, the initial rise in the action potential is associated with an increase in membrane permeability for Na+, and the plateau in the action potential is due to an increase in membrane permeability for Ca2+ ions.

ABOUT THE NATURE OF IONIC PERMEABILITY OF THE MEMBRANE. ION CHANNELS The considered changes in the ionic permeability of the membrane during the generation of an action potential are based on the processes of opening and closing of specialized ion channels in the membrane, which have two important properties: 1) selectivity towards certain ions;

2) electrical excitability, i.e. the ability to open and close in response to changes in membrane potential. The process of opening and closing a channel is probabilistic in nature (the membrane potential only determines the probability of the channel being in an open or closed state).

Just like ion pumps, ion channels are formed by protein macromolecules that penetrate the lipid bilayer of the membrane. The chemical structure of these macromolecules has not yet been deciphered, so ideas about the functional organization of channels are still being built mainly indirectly - based on the analysis of data obtained from studies of electrical phenomena in membranes and the influence of various chemical agents (toxins, enzymes, drugs, etc.) on the channels. etc.). It is generally accepted that the ion channel consists of the transport system itself and the so-called gating mechanism (“gate”), controlled by the electric field of the membrane. The “gate” can be in two positions: it is completely closed or completely open, so the conductivity of a single open channel is a constant value.

The total conductivity of the membrane for a particular ion is determined by the number of simultaneously open channels permeable to a given ion.

This position can be written as follows:

where gi is the total permeability of the membrane for intracellular ions;

N is the total number of corresponding ion channels (in a given region of the membrane);

a - is the proportion of open channels;

y is the conductivity of a single channel.

According to their selectivity, electrically excitable ion channels of nerve and muscle cells are divided into sodium, potassium, calcium, and chloride. This selectivity is not absolute:

the name of the channel indicates only the ion for which the channel is most permeable.

Through open channels, ions move along concentration and electrical gradients. These ion flows lead to changes in the membrane potential, which in turn changes the average number of open channels and, accordingly, the magnitude of ionic currents, etc. Such a circular connection is important for the generation of an action potential, but it makes it impossible to quantify the dependence of ionic conductances on the magnitude of the generated potential. To study this dependence, the “potential fixation method” is used. The essence of this method is to forcibly maintain the membrane potential at any given level. Thus, by supplying the membrane with a current equal in magnitude, but opposite in sign to the ionic current passing through open channels, and measuring this current at different potentials, researchers are able to trace the dependence of the potential on the ionic conductivities of the membrane (Fig. 7). Time course of changes in sodium (gNa) and potassium (gK) membrane permeability upon depolarization of the axon membrane by 56 mV.

a - solid lines show permeability during long-term depolarization, and dotted lines - during membrane repolarization after 0.6 and 6.3 ms;

b dependence of the peak value of sodium (gNa) and steady-state level of potassium (gK) permeability on the membrane potential.

Rice. 8. Schematic representation of an electrically excitable sodium channel.

Channel (1) is formed by a macromolecule of protein 2), the narrowed part of which corresponds to a “selective filter”. The channel has activation (m) and inactivation (h) “gates”, which are controlled by the electric field of the membrane. At the resting potential (a), the most probable position is “closed” for the activation gate and the “open” position for the inactivation gate. Depolarization of the membrane (b) leads to the rapid opening of the t-“gate” and the slow closing of the h-“gate”, therefore, at the initial moment of depolarization, both pairs of “gates” are open and ions can move through the channel in accordance with There are substances with their concentrations of ionic and electrical gradients. With continued depolarization, the inactivation “gate” closes and the channel goes into the inactivation state.

EDUCATIONAL LITERATURE

Moscow “Medicine” 1985

For medical students

person

Edited by

member-corr. USSR Academy of Medical Sciences G. I. KOSITS KO G"O

third edition,

revised and expanded

Approved by the Main Directorate of Educational Institutions of the Ministry of Health of the USSR as a textbook for students of medical institutes

>BK 28.903 F50

/DK 612(075.8) ■

[E, B. BABSCII], V. D. GLEBOVSKY, A. B. KOGAN, G. F. KOROTKO,

G. I. KOSITSKY, V; M, POKROVSKY, Y. V. NATOCHIN, V. P. SKIPETROV, B. I. KHODOROV, A. I. SHAPOVALOV, I. ​​A. SHEVELEV

Reviewer Y..D.Boyenko, prof., head Department of Normal Physiology, Voronezh Medical Institute named after. N. N. Burdenko

UK1 5L4

1yuednu «i--c; ■ ■■ ^ ■ *

Human physiology/Ed. G.I. Kositsky. - F50 3rd ed., revised. and additional - M.: "Medicine", 1985. 544 e., ill.

In lane: 2 r. 20 k. 150,000 copies.

The third edition of the textbook (the second was published in 1972) was written in accordance with the achievements of modern science. New facts and concepts are presented, new chapters are included: “Features of higher nervous activity of man”, “Elements of labor physiology”, mechanisms of training and adaptation”, sections covering issues of biophysics and physiological cybernetics have been expanded. Nine chapters of the textbook have been redrawn, the rest largely reworked: .

The textbook corresponds to the program approved by the USSR Ministry of Health and is intended for students of medical institutes.

f ^^00-241 BBK 28.903

039(01)-85

(6) Publishing house "Medicine", 1985

PREFACE

12 years have passed since the previous edition of the textbook “Human Physiology” The responsible editor and one of the authors of the book, Academician of the Academy of Sciences of the Ukrainian SSR E.B. Babsky, according to whose manuals many generations of students studied physiology, have passed away. -

The team of authors of this publication includes well-known specialists in the relevant sections of physiology: corresponding member of the USSR Academy of Sciences, prof. A.I. Shapovalov" and Prof. Yu, V. Natochin (heads of laboratories of the I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the USSR Academy of Sciences), Prof. V.D. Glebovsky (head of the Department of Physiology of the Leningrad Pediatric Medical Institute) ; prof. , A.B. Kogan (Head of the Department of Human and Animal Physiology and Director of the Institute of Neurocybernetics of Rostov State University), prof. G. F. Korotks (Head of the Department of Physiology, Andijan Medical Institute), pr. V.M. Pokrovsky (Head of the Department of Physiology, Kuban Medical Institute), prof. B.I. Khodorov (head of the laboratory of the A.V. Vishnevsky Institute of Surgery of the USSR Academy of Medical Sciences), prof. I. A. Shevelev (head of the laboratory of the Institute of Higher Nervous Activity and Neurophysiology of the USSR Academy of Sciences). - I

Over the past time, a large number of new facts, views, theories, discoveries and directions of our science have appeared. In this regard, 9 chapters in this edition had to be written anew, and the remaining 10 chapters had to be revised and supplemented. At the same time, to the extent possible, the authors tried to preserve the text of these chapters.

The new sequence of presentation of the material, as well as its combination into four main sections, is dictated by the desire to give the presentation logical harmony, consistency and, as far as possible, to avoid duplication of material. ■ -

The content of the textbook corresponds to the physiology program approved in 1981. Critical comments about the project and the program itself, expressed in the resolution of the Bureau, Department of Physiology of the USSR Academy of Sciences (1980) and at the All-Union Meeting of Heads of Physiology Departments of Medical Universities (Suzdal, 1982), were also taken into account. In accordance with the program, chapters were introduced into the textbook that were missing in the previous edition: “Features of higher nervous activity of man” and “Elements of labor physiology, mechanisms of training and adaptation,” and sections covering issues of particular biophysics and physiological cybernetics were expanded. The authors took into account that in 1983 a textbook of biophysics for students of medical institutes was published (edited by Prof. Yu A. Vladimirov) and that the elements of biophysics and cybernetics are presented in the textbook of Prof. A.N. Remizov “Medical and biological physics”.

Due to the limited volume of the textbook, it was necessary, unfortunately, to omit the chapter “History of Physiology”, as well as excursions into history in individual chapters. Chapter 1 gives only outlines of the formation and development of the main stages of our science and shows its importance for medicine.

Our colleagues provided great assistance in creating the textbook. At the All-Union Meeting in Suzdal (1982), the structure was discussed and approved, and valuable suggestions were made regarding the content of the textbook. Prof. V.P. Skipetrov revised the structure and edited the text of the 9th chapter and, in addition, wrote its sections relating to blood coagulation. Prof. V. S. Gurfinkel and R. S. Person wrote the subsection of the 6th chapter “Regulation of movements”. Assoc. N. M. Malyshenko presented some new materials for Chapter 8. Prof. I.D.Boenko and his staff expressed many useful comments and suggestions as reviewers.

Employees of the Department of Physiology II MOLGMI named after N. I. Pirogova prof. L. A. M. iyutina, associate professors I. A. Murashova, S. A. Sevastopolskaya, T. E. Kuznetsova, candidate of medical sciences / V. I. Mongush and L. M. Popova took part in discussion of the manuscript of some chapters, (we would like to express our deep gratitude to all these comrades.

The authors are fully aware that in such a difficult task as creating a modern textbook, shortcomings are inevitable and therefore will be grateful to everyone who makes critical comments and suggestions about the textbook. "

Corresponding member of the USSR Academy of Medical Sciences, prof. G. I. KOSITSKY

Chapter 1 (- v

PHYSIOLOGY AND ITS IMPORTANCE

Physiology(from rpew.physis - nature and logos - teaching) - the science of the life activity of the whole organism and its individual parts: cells, tissues, organs, functional systems. Physiology seeks to reveal the mechanisms of the functions of a living organism, their relationship with each other, regulation and adaptation to the external environment, origin and formation in the process of evolution and individual development of the individual

Physiological patterns are based on data on the macro- and microscopic structure of organs and tissues, as well as on the biochemical and biophysical processes occurring in cells, organs and tissues. Physiology synthesizes specific information obtained by anatomy, histology, cytology, molecular biology, biochemistry, biophysics and other sciences, combining them into a single system of knowledge about the body. Thus, physiology is a science that carries out systems approach, that is, the study of the body and all its elements as systems. Using a systematic approach, we orient the researcher, first of all, to reveal the integrity of the object and its supporting mechanisms, i.e., to identify diverse types of connections complex object and reducing them to unified theoretical picture.

An object studying physiology - a living organism, the functioning of which as a whole is not the result of a simple mechanical interaction of its constituent parts. The integrity of the organism does not arise as a result of the influence of some supramaterial entity, which unquestioningly subjugates all the material structures of the organism. Similar interpretations of the Integrity of the organism existed and still exist in the form of a limited mechanistic ( metaphysical) or no less limited idealistic ( vitalistic) approach to the study of life phenomena. The errors inherent in both approaches can only be overcome by studying these problems with dialectical-materialist positions. Therefore, the patterns of activity of the organism as a whole can be understood only on the basis of a consistently scientific worldview. For its part, the study of physiological laws provides rich factual material illustrating a number of provisions of dialectical materialism. The connection between physiology and philosophy is thus two-way.

Physiology and medicine /

By revealing the basic mechanisms that ensure the existence of an entire organism and its interaction with the environment, physiology makes it possible to clarify and study the causes, conditions and nature of disturbances and the activity of these mechanisms during illness. It helps to determine the ways and means of influencing the body, with the help of which its functions can be normalized, i.e. restore health. Therefore physiology is theoretical basis of medicine, physiology and medicine are inseparable." The doctor assesses the severity of the disease by the degree of functional disorders, i.e., by the magnitude of deviations from the norm of a number of physiological functions. Currently, such deviations are measured and assessed quantitatively. Functional (physiological) studies are the basis of clinical diagnosis, as well as a method for assessing the effectiveness of treatment and prognosis of diseases. By examining the patient, establishing the degree of impairment of physiological functions, the doctor sets himself the task of returning e+functions to normal.

However, the importance of physiology for medicine is not limited to this. The study of the functions of various organs and systems made it possible simulate These functions are performed with the help of devices, devices and devices created by human hands. In this way the artificial kidney (hemodialysis machine). Based on the study of the physiology of heart rhythm, a device was created for Electr about stimulation heart, ensuring normal cardiac activity and the possibility of returning to work for patients with severe heart damage. Manufactured artificial heart and devices artificial blood circulation(machining “heart - lungs”) ^allowing the patient’s heart to be switched off during a complex operation on the heart. There are devices for defib-1lations, which restore normal cardiac activity in case of fatal -> 1X violations of the contractile function of the heart muscle.

Research in the field of respiratory physiology made it possible to construct a controlled artificial respiration(“iron lungs”) Devices have been created with the help of which it is possible to turn off the patient’s breathing for a long time. In conditions of terations, or: for years to maintain the life of the body in case of damage to the respiratory system. Knowledge of the physiological laws of gas exchange and gas transport helped to create installations for hyperbaric oxygenation. It is used for fatal lesions of the system: the blood, as well as the respiratory and cardiovascular systems, and based on the laws of brain physiology, methods for a number of complex neurosurgical operations have been developed. Thus, electrodes are implanted into the cochlea of ​​a deaf person, according to which electrical impulses from artificial sound receivers, which restore hearing to a certain extent.":

These are just a few examples of the use of the laws of physiology in the clinic, but the significance of our science goes far beyond the boundaries of just medical medicine.

The role of physiology is ensuring human life and activity in various conditions

The study of physiology is necessary for scientific substantiation and creation of conditions for a healthy lifestyle that prevents diseases. Physiological patterns are the basis scientific organization of labor in modern production. Physiojugia made it possible to develop a scientific basis for various individual training modes and sports loads that underlie modern sports achievements - 1st. And not only sports. If you need to send a person into space or drain him from the depths of the ocean, undertake an expedition to the north and south poles, reach the peaks of the Himalayas, explore the tundra, taiga, desert, place a person in conditions of extremely high or low temperatures, move him to different time zones, etc. climatic conditions, then physiology helps to justify and ensure everything necessary for human life and work in such extreme conditions..

Physiology and technology

Knowledge of the laws of physiology was required not only for scientific organization, but also for increasing labor productivity. Over billions of years of evolution, nature is known to have achieved the highest perfection in the design and control of the functions of living organisms. The use in technology of principles, methods and methods operating in the body opens up new prospects for technical progress. Therefore, at the intersection of physiology and technical sciences, a new science was born - bionics.

The successes of physiology contributed to the creation of a number of other fields of science.

DEVELOPMENT OF PHYSIOLOGICAL RESEARCH METHODS

Physiology was born as a science experimental. All it obtains data through direct study of the vital processes of animal and human organisms. The founder of experimental physiology was the famous English physician William Harvey. v" ■

- “Three hundred years ago, amid the deep darkness and now difficult to imagine confusion that reigned in ideas about the activities of animal and human organisms, but illuminated by the inviolable authority of the scientific classic. heritage; physician William Harvey spied on one of the most important functions of the body - blood circulation and thereby laid the foundation for a new department of precise human knowledge - animal physiology,” wrote I.P. Pavlov. However, for two centuries after the discovery of blood circulation by Harvey, the development of physiology occurred slowly. It is possible to list relatively few fundamental works of the 17th-18th centuries. This is the opening of capillaries(Malpighi), formulation of the principle .reflex activity of the nervous system(Descartes), measurement of quantity blood pressure(Hels), wording of the law conservation of matter(M.V. Lomonosov), discovery of oxygen (Priestley) and commonality of combustion and gas exchange processes(Lavoisier), opening " animal electricity", i.e. e . the ability of living tissues to generate electrical potentials (Galvani), and some other works:

Observation as a method of physiological research. The relatively slow development of experimental physiology over the two centuries after Harvey's work is explained by the low level of production and development of natural science, as well as the difficulties of studying physiological phenomena through their usual observation. This methodological technique was and remains the cause of numerous errors, since the experimenter must conduct experiments, see and remember many

HjE. VVEDENSKY(1852-1922)

to: ludwig

: your complex processes and phenomena, which is a difficult task. The difficulties created by the method of simple observation of physiological phenomena are eloquently evidenced by the words of Harvey: “The speed of cardiac motion does not make it possible to distinguish how systole and diastole occur, and therefore it is impossible to know at what moment / in which part expansion and contraction occur. Indeed, I could not distinguish systole from diastole, since in many animals the heart appears and disappears in the blink of an eye, with the speed of lightning, so it seemed to me that once there was systole and here there was diastole, and another time it was the other way around. There is difference and confusion in everything.”

Indeed, physiological processes are dynamic phenomena. They are constantly developing and changing. Therefore, it is possible to directly observe only 1-2 or, at best, 2-3 processes. However, in order to analyze them, it is necessary to establish the relationship of these phenomena with other processes that, with this method of research, remain unnoticed. In this regard, simple observation of physiological processes as a research method is a source of subjective errors. Usually observation allows us to establish only the qualitative side of phenomena and makes it impossible to study them quantitatively.

An important milestone in the development of experimental physiology was the invention of the kymograph and the introduction of the method of graphically recording blood pressure by the German scientist Karl Ludwig in 1843.

Graphic registration of physiological processes. The graphic recording method marked a new stage in physiology. It made it possible to obtain an objective record of the process being studied, which minimized the possibility of subjective errors. In this case, the experiment and analysis of the phenomenon under study could be carried out in two stages: During the experiment itself, the experimenter's task was to obtain high-quality recordings - curves. The analysis of the obtained data could be carried out later, when the experimenter’s attention was no longer distracted by the experiment. The graphic recording method made it possible to record simultaneously (synchronously) not one, but several (theoretically unlimited number) physiological processes. "..

Quite soon after the invention of blood pressure recording, methods for recording heart and muscle contractions were proposed (Engelman), and a method was introduced; stuffy transmission (Marey's capsule), which made it possible to record sometimes at a considerable distance from the object a number of physiological processes in the body: respiratory movements of the chest and abdominal cavity, peristalsis and changes in the tone of the stomach and intestines, etc. A method was proposed for recording vascular tone (Mosso plethysmography), changes in the volume of various internal organs - oncometry, etc.

Research of bioelectric phenomena. An extremely important direction in the development of physiology was marked by the discovery of “animal electricity”. The classic “second experiment” of Luigi Galvani showed that living tissues are a source of electrical potentials that can act on the nerves and muscles of another organism and cause muscle contraction. Since then, for almost a century, the only indicator of potentials generated by living tissues [bioelectric potentials), was a frog neuromuscular preparation. He helped to discover the potentials generated by the Heart during its activity (the experience of K. Elliker and Müller), as well as the need for continuous generation of electrical potentials for constant contraction of the Muscles (the experience of “secondary regeneration.” Mateuchi). It became clear that bioelectric potentials are not random (side) phenomena in the activity of living tissues, but signals with the help of which commands are transmitted in the body to the nervous system! and from it: to muscles and other organs and thus living tissues I interact" with each other using "electric language". „

It was possible to understand this “language” much later, after the invention of physical devices that captured bioelectric potentials. One of the first such devices! there was a simple telephone. The remarkable Russian physiologist N.E. Vvedensky, using the telephone, discovered a number of the most important physiological properties of nerves and muscles. Using a telephone, we were able to listen to bioelectric potentials, i.e. explore their path\observations. A significant step forward was the invention of a technique for objective graphic recording of bioelectric phenomena. Dutch physiologist Einthoweg invented string galvanometer- a device that made it possible to register, on photo paper, the electrical potentials arising during the activity of the heart - an electrocardiogram (ECG). In our country, the pioneer of this method was the largest physiologist, student of I.M. Sechenov and I.P. Pavlov, A.F. Samoilov, who worked for some time in the Einthoven laboratory in Leiden, ""

Very soon the author received a response from Einthoven, who wrote: “I exactly fulfilled your request and read the letter to the galvanometer. Undoubtedly/ he listened and accepted with pleasure and joy everything that you wrote. He had no idea that he had done so much for humanity. But at the point where Zy says that he can’t read, he suddenly became furious... so much so that my family and I even got excited. He shouted: What, I can’t read? This is a terrible lie. Am I not reading all the secrets of the heart? "

Indeed, electrocardiography very soon moved from physiological laboratories to the clinic as a very advanced method for studying the condition of the heart, and many millions of patients today owe their lives to this method.

Subsequently, the use of electronic amplifiers made it possible to create compact electrocardiographs, and telemetry methods make it possible to record the ECG of astronauts in orbit, of athletes on the track and of patients in remote areas, from where the ECG is transmitted via telephone wires to large cardiology institutions for comprehensive analysis.

"Objective graphic registration of bioelectric potentials served as the basis for the most important section of our science - electrophysiology. A major step forward was the proposal of the English physiologist Adrian to use electronic amplifiers to record biocentric phenomena. The Soviet scientist V.V. Pravdicheminsky was the first to register the biocurrents of the brain - he received electro-chephalogram(EEG). This method was later improved by the German scientist Ber-IpoM. Currently, electroencephalography is widely used in the clinic, as well as graphic recording of electrical potentials of muscles ( electromyography ia), nerves and other excitable tissues and organs. This made it possible to conduct a fine-grained assessment of the functional state of these organs and systems. For physiology itself, smear methods were also of great importance; they made it possible to decipher the functional and structural mechanisms of the activity of the nervous system and other tissue organs, the mechanisms of regulation of physiological processes.

An important milestone in the development of electrophysiology was the invention microelectrodes, e. the thinnest electrodes, the diameter of the tip of which is equal to fractions of a micron. These electrodes, using appropriate micromanipulator devices, can be introduced directly into the cell and bioelectric potentials can be recorded intracellularly. Microelectrodes made it possible to decipher the mechanisms of generation of biopotentials, i.e. processes occurring in cell membranes. Membranes are the most important formations, since through them the processes of interaction of cells in the body and individual elements of the cell with each other are carried out. The science of the functions of biological membranes - membranepology - has become an important branch of physiology.

Methods of electrical stimulation of organs and tissues. A significant milestone in the development of physiology was the introduction of the method of electrical stimulation of organs and tissues. Living organs and tissues are capable of responding to any influence: thermal, mechanical, chemical, etc., electrical stimulation by its nature is closest to the “natural language” with the help of which living systems exchange information. The founder of this method was the German physiologist Dubois-Reymond, who proposed his famous “sleigh apparatus” (induction coil) for dosed electrical stimulation of living tissues.

Currently they use electronic stimulators, allowing you to generate electrical impulses of any shape, frequency and strength. Electrical stimulation has become an important method for studying the functions of organs and tissues. This method is also widely used in the clinic. Designs of various electronic stimulators have been developed that can be implanted into the body. Electrical stimulation of the heart has become a reliable way to restore the normal rhythm and functions of this vital organ and has returned hundreds of thousands of people to work. Electrical stimulation of skeletal muscles has been successfully used, and methods of electrical stimulation of areas of the brain using implanted electrodes are being developed. The latter, using special stereotake devices, are introduced into strictly defined nerve centers (with an accuracy of fractions of a millimeter). This method, transferred from physiology to the clinic, allowed to cure thousands of severe neurological patients and obtain a large amount of important data on the mechanisms of the human brain (N. P. Bekhtereva). We talked about this not only to give an idea of ​​some methods of physiological research, but also to illustrate the importance of physiology for the clinic. . .

In addition to recording electrical potentials, temperature, pressure, mechanical movements and other physical processes, as well as the results of the impact of these processes on the body, chemical methods are widely used in physiology.

Chemical methodsV physiology. The language of electrical signals is not the most universal in the body. The most common is the chemical interaction of life processes (chains of chemical processes, occurring in living tissues). Therefore, a branch of chemistry arose that studies these processes—physiological chemistry. Today it has turned into an independent science - biological. The chemist's data reveal the molecular mechanisms of physiological processes. The physiologist widely uses chemical methods in his experiments, as well as methods that arose at the intersection of chemistry, physics and biology. These methods have given rise to new branches of science, for example biophysics, studying the physical side of physiological phenomena.

The physiologist widely uses the method of labeled atoms. Modern physiological research also uses other methods borrowed from the exact sciences. They provide truly invaluable information when analyzing certain mechanisms of physiological processes. . ; ■

Electrical recording of non-electrical quantities. Significant progress in physiology today is associated with the use of radioelectronic technology. Apply sensors- converters of various non-electrical phenomena and quantities (motion, pressure, temperature, concentration of various substances, ions, etc.) into electric potentials, which are then amplified by electronic ones amplifiers and register oscilloscopes. A huge number of different types of such recording devices have been developed, which make it possible to record many physiological processes on an oscilloscope. A number of devices use additional influences on the body (ultrasonic or electromagnetic waves, high-frequency electrical vibrations, etc.). In such cases, record the change in the values ​​of these parameters; influences that change certain physiological functions. The advantage of such devices is that the transducer-sensor can be mounted not on the organ being studied, but on the surface of the body. Waves and vibrations affecting the body* And etc. penetrate the body and, after influencing the function under study, or "org.g" are recorded by a sensor. For example, ultrasonic flow meters, determining the speed of blood flow in the vessels, rheographs And rerplethysmographs, recording changes in the amount of blood supply to various parts of the body, and many other devices. Their advantage is the ability to study the body V any time without preliminary operations. In addition, such studies do not harm the body. Most/modern methods of physiological research V clinic is based on these principles. In the USSR, the initiator of the use of radio-electronic technology for physiological research was Academician V.V. Parin. . "■

A significant advantage of such registration methods is that the physiological process is converted by the sensor into electrical vibrations, and the latter can be amplified and transmitted by wire or radio to any distance from the object being studied. This is how the methods arose telemetry, with the help of which it is possible in a ground laboratory to register physiological processes in the body of an astronaut in orbit, a pilot in flight, an athlete, on the highway, a worker during work, etc. The registration itself in no way interferes with the activities of the subjects. . . . : ,

However, the deeper the analysis of processes, the greater the need for synthesis arises, i.e. creation, from individual elements, of a whole picture of “phenomena.”

The task of physiology is to, along with deepening analysis continuously implement and synthesis, give a holistic view of the body as a system. . ■<

The laws of physiology allow us to understand the reaction of the body (as an integral system) and all its subsystems under certain conditions, under certain influences, etc.! Therefore, any method of influencing the body, before entering clinical practice, undergoes comprehensive testing in physiological experiments.

Acute experimental method. The progress of science is associated not only with the development of experimental technology and research methods. It greatly depends on the evolution of the thinking of physiologists, on the development of methodological and methodological approaches to the study of physiological phenomena. From the beginning until the 80s of the last century, isiology remained a science analytical. She divided the body into separate organs and systems and studied their activity in isolation. The main methodological method of analytical physiology was experiments on isolated organs, or so-called acute experiences. Moreover, in order to gain access to “any internal organ” or system, the physiologist had to engage in vivisection (live cutting). : 1 "

The animal was tied to a machine and a complex and painful operation was performed, it was hard work, but science did not know any other way to penetrate into the depths of the body (it was not only the moral side of the problem. Cruel torture, unbearable gradations to which the Organism was subjected, grossly violated the normal course of physiological phenomena and did not allow us to understand the essence of the processes occurring in natural conditions, normally." The use of anesthesia, as well as other methods of pain relief, did not help significantly. Fixation of the animal, exposure to narcotic substances, surgery, blood loss - all this completely changed and disrupted the normal course of life. A vicious circle was formed. In order to study one or another process or function of an internal organ or system, it was necessary to penetrate into the depths of the organ. aism, and the very attempt of such penetration disrupted the flow of vital processes, for the study of which the experiment was undertaken.In addition, the study of isolated organs did not give an idea of ​​their true function in the conditions of a whole (damaged organism. "

Chronic experiment method. The greatest merit of Russian science in the history of physiology was the fact that one of its most talented and brightest. representatives I.P. Tavlov managed to find a way out of this impasse. I. P. Pavlov experienced the disadvantages of analytical physiology and acute experiment very painfully. He found a way to look deep into the body without violating its integrity. This was the method chronic experiment, based on "physiological surgery".

On an anesthetized animal, under conditions of sterility and compliance with the rules of surgical technique, a complex operation was previously carried out, which made it possible to gain access to one or another internal organ, a “window” was made into the sweat organ, a fistula tube was implanted, or a gland tract was brought out and sutured to the skin. The experiment itself began many days later, when the wound healed, the animal recovered and, in terms of the nature of the physiological processes, was practically no different from a normal healthy one. Thanks to the applied fistula, it was possible to study for a long time the course of certain physiological processes in natural conditions of behavior.■ . . . .

PHYSIOLOGY OF THE WHOLE ORGANISM " ",

It is well known that science develops depending on the success of methods.

Pavlov’s method of chronic experiment created a fundamentally new science - the physiology of the whole organism, synthetic physiology, which was able to identify the influence of the external environment on physiological processes, detect changes in the functions of various organs and systems to ensure the life of the body in various conditions.

With the advent of modern technical means for studying life processes, it has become possible to study without preliminary surgical operations functions of many internal organs not only in animals, but also in humans.“Physiological surgery” as a methodological technique in a number of sections of physiology has turned out to be supplanted by modern methods of bloodless experiment. But the point is not in this or that specific technical technique, but in the methodology of physiological thinking. I. P. Pavlov

Cybernetics (from Greek. kyb" ernetike- art of management) - the science of managing automated processes. Control processes, as is known, V are carried out by signals carrying a certain information. In the body, such signals are nerve impulses of an electrical nature, as well as various chemical substances;

Cybernetics studies the processes of perception, encoding, processing, storage and reproduction of information. In the body, there are special devices and systems for these purposes (receptors, nerve fibers, nerve cells, etc.). 1 Technical cybernetic devices made it possible to create models, reproducing some functions of the nervous system. However, the functioning of the brain as a whole is not yet amenable to such modeling, and further research is needed.

The union of cybernetics and physiology arose only three decades ago, but during this time the mathematical and technical arsenal of modern cybernetics has provided significant advances in the study and modeling of physiological processes.

Mathematics and computer technology in physiology. Simultaneous (synchronous) registration of physiological processes allows for quantitative analysis and study of the interaction between various phenomena. This requires precise mathematical methods, the use of which also marked a new important stage in the development of physiology. Mathematization of research allows the use of electronic computers in physiology. This not only increases the speed of information processing, but And makes it possible to carry out such processing immediately at the time of the experiment, which allows you to change its course and the objectives of the research itself in accordance with the results obtained.

I. P. PAVLOV (1849-1936)

created a new methodology, and physiology developed as a synthetic science and it became organically inherent systems approach. . "

A complete organism is inextricably linked with the external environment surrounding it, and therefore, as he also wrote; I. M. Sechenov^ The scientific definition of an organism must also include the environment that influences it. The physiology of the whole organism studies not only the internal mechanisms of self-regulation of physiological processes, but also the mechanisms that ensure continuous interaction and inextricable unity of the organism with the environment.

Regulation of vital processes, as well as the interaction of the organism with the environment, is carried out on the basis of principles common to regulatory processes in machines and automated production. These principles and laws are studied by a special field of science - cybernetics.

Physiology and cybernetics

\Thus, the spiral in the development of physiology seems to have ended. At the dawn of this science, research, analysis and evaluation of the results were carried out by the experimenter simultaneously in the process of observation, directly during the experiment itself. Graphic recording made it possible to separate these processes in time and process and analyze the results after the end of the experiment. Radio electronics and cybernetics made it possible to once again combine the analysis and processing of results with the conduct of the experiment itself, but on a fundamentally different basis: the interaction of many different physiological processes is simultaneously studied and the results of such interaction are analyzed quantitatively. This made it possible to

) the so-called controlled automatic experiment, in which a computing machine helps the researcher not only analyze the results, but also understand the course of the experiment and the formulation of problems, as well as the types of influence on the body, depending on the nature of the body’s reactions that arise directly; during the reading. Physics, mathematics, cybernetics and other exact sciences have re-equipped physiology and provided the doctor with a powerful arsenal of modern technical means for accurately assessing the functional state of the body and for influencing the body.

Mathematical modeling in physiology. Knowledge of physiological laws and quantitative relationships between various physiological processes made it possible to create their mathematical models. With the help of such models, these processes are reproduced on electronic computers, exploring various reaction options, i.e. their possible future changes under certain influences on the body (medicines, physical factors or extreme environmental conditions) - Already now, the union of physiology and cybernetics has proven useful in carrying out heavy surgical operations and in other emergency conditions requiring an accurate assessment both the current state of the most important physiological processes of the body, and the anticipation of possible changes. This approach allows us to significantly increase the reliability of the “human factor” in difficult and critical parts of modern production.

Physiology of the 20th century. has made significant progress not only in the field of revealing the mechanisms of vital processes and controlling these processes. She made a breakthrough into the most complex and mysterious area - into the area of ​​psychic phenomena.

The physiological basis of the psyche - the higher nervous activity of humans and animals - has become one of the important objects of physiological research. ;

OBJECTIVE STUDY OF HIGHER NERVOUS ACTIVITY

I.M. Sechenov was the first physiologist in the world who dared to imagine behavior based on the reflex principle, i.e. based on the mechanisms of nervous activity known in physiology. In his famous book “Reflexes of the Brain,” he showed that no matter how complex the external manifestations of human mental activity may seem to us, they sooner or later come down to just one muscle movement. ^Whether a child smiles at the sight of a new toy, whether Garibaldi laughs when he is punished for being too fond of his family, whether Newton invents world laws and writes IX on paper, whether a Girl trembles at the thought of her first date, the end result of the thought is always a single-muscular movement.” , - wrote I.M. Sechenov.

Analyzing the formation of a child’s thinking, I.M. Sechenov showed step by step. -JTO this thinking is formed as a result of the influences of the external environment, combined with each other in various combinations, causing the formation of different associations - Our thinking (spiritual life) is naturally formed under the influence of environmental conditions and the brain is an “organ that accumulates and reflects these influences. No matter how complex the manifestations of our Mental life may seem to us, our internal psychological make-up is a logical result of the conditions of upbringing, environmental influences. 999/1000 of a person’s mental content depends on the conditions of upbringing, environmental influences in the broad sense of the word, wrote I.M. . Sechenov, - and only 1/1000 it is determined by innate factors. Thus, it was first extended to the most complex area of ​​life phenomena, to the processes of human spiritual life principle of determinism- the basic principle of the materialistic worldview, I.M. Sechenov wrote that someday a physiologist will learn to analyze the external manifestations of brain activity as accurately as a physicist can analyze

strike a musical chord. I.M. Sechenov’s book was a work of genius, affirming materialistic positions in the most difficult spheres of human spiritual life.

Sechenov's attempt to substantiate the mechanisms of brain activity was a purely theoretical attempt. The next step was necessary - experimental studies of the physiological mechanisms underlying mental activity and behavioral reactions. And this step was taken by I.P. Pavlovik.

The fact that it was I.P. Pavlov, and not anyone else, who became the heir to the ideas of I.M. Sechenov and was the first to penetrate the basic secrets of the work of the higher parts of the brain is not accidental. To that; led by the logic of his experimental physiological studies. Studying the vital processes in the body under conditions of natural animal behavior, I. P. Pavlov drew attention to the important role mental factors, influencing all physiological processes. The observation of I. P. Pavlov did not escape the fact that I. M. SECHENOV

J ■ ^ ". P829-1OD5Ъ

saliva, gastric juice and other digestives. ^^^i^v/

body juices begin to be released from the animal not only at the moment of eating, but long before eating at the sight of food or the sound of the steps of the attendant who usually feeds the animal. I. P. Pavlo! drew attention to the fact that appetite, the passionate desire for food, is as powerful a juice-secreting agent as food itself. Appetite, desire," mood, experiences, feelings - all these were mental phenomena. Before I. P. Pavlov, physiologists< изучались. И."П. Павлов же увидев, что игнорировать эти явления фйзиолог не вправе так как они властно вмешиваются в течение физйологических процессов, меняя их харак тер. Поэтому физиолог обязан был их изучать. Но как? До И. П. Павлова эти явление рассматривались наукой, которая называется зоопсихология.

Having turned to this science, I.P. Pavlov had to move away from the solid ground of physiological facts and enter the realm of fruitless and groundless fortune-telling regarding the apparent mental state of animals. To explain human behavior, the methods used in psychology are legitimate, since a person can always report his feelings, moods, experiences, etc. Animal psychologists blindly transferred data obtained from human examinations to animals, and also talked about “feelings,” “moods,” “experiences,” “desires,” etc. in the animal, without being able to check whether this is true or not. For the first time in Pavlov's laboratories, as many opinions arose about the mechanisms of the same facts as there were observers who saw these facts. Each of them interpreted them in his own way, and there was no way to verify the correctness of any of the interpretations. I.P. Pavlov realized that such interpretations were meaningless and therefore took a decisive, truly revolutionary step. Without trying to guess about certain internal mental states of the animal, he began study animal behavior objectively, comparing certain effects on the body with the body’s responses. This objective method made it possible to identify the laws underlying the behavioral reactions of the body.

The method of objectively studying behavioral reactions created a new science - physiology of higher nervous activity with its exact knowledge of the processes occurring in the nervous system under +ex or other influences of the external environment. This Science has given a lot for understanding the essence of the mechanisms of human mental activity.

The physiology of higher nervous activity created by I. P. Pavlov became the natural scientific basis of psychology. It became a natural scientific basis Lenin Yuria reflections, has vital importance in philosophy, medicine, pedagogy and in all those sciences that one way or another face the need to study the inner (spiritual) world of man:

The importance of the physiology of higher nervous activity for medicine. The teaching of I. P. auloz on higher nervous activity is of great practical importance. I know. that a patient is cured not only by medicine, a scalpel or a procedure, but also the word oacha, trust in him, a passionate desire to get well. All these facts were known to Hippocrates and Avicenna. However, for thousands of years they were perceived as proof of the existence of a powerful “God-given soul” that subjugates the mortal body.” The teachings of I. P. Pavlov tore off the veil of mystery from these facts, / it was clear that the seemingly magical influence of talismans, a sorcerer or the spells of a shaman is nothing more than an example of the influence of the higher parts of the brain: and internal organs and regulation of all life processes.; The nature of that influence is determined by the effect on the body of the surrounding guslbvii,” important; the greatest of which for humans are social conditions in particular, the exchange of ideas in human society using words. For the first time in the history of science, I.P. Pavlov showed that the power of words lies in the fact that words and speech represent a special system of signals, inherent only to humans, which naturally changes behavior and mental status. Paul's teaching expelled idealism from the very last, seemingly inaccessible refuge - the idea of ​​a God-given “soul”; It put into the hands (developing a powerful weapon, giving it the opportunity to use it correctly.) in a word, showing the most important role moral impact on the patient for the success of treatment. ■

CONCLUSION

D. A. UKHTOMSKY - " L. A. ORBELI

(1875-1942) . (1882-1958)

I.P. Pavlov can rightfully be considered the founder of modern physiojugia of the whole organism. Other outstanding Soviet physiologists also made a major contribution to its development. A. A. Ukhtomsky created the doctrine of the dominant as the main principle of the activity of the central nervous system (CNS). L. A. Orbeli founded the evolutionary

K. M. BYKOV (1886-1959)

P: K. ANOKHIN ■ (1898-1974)

I. S. BERITASHVILI (1885-1974)

tional physiology. He authored fundamental works on the adaptive-trophic function of the sympathetic nervous system. K-M.. Bykov revealed the presence of conditioned reflex regulation of the functions of internal organs, showing that autonomic functions are not autonomous, that they are subject to the influence of higher “divisions of the central nervous system, and can change under the influence of conditioned signals. For a person, the most important conditioned signal is the word. This signal is capable of changing the activity of internal organs, which is of utmost importance for medicine (psychotherapy, deontology, etc.).

P.K. Anokhin developed the doctrine of a functional system - a universal scheme for regulating physiological processes and behavioral reactions of the body.

The leading neurophysiologist I. S. Beritov (Beritashvili) created a number of original directions in the physiology of the neuromuscular and central nervous systems. L. S. Stern is the author of the doctrine of the hematoencephalological barrier and histohematic barriers - regulators of the immediate internal media of organs and tissues. V.V. Parin made major discoveries in the field of regulation of the cardiovascular system (Parin reflex). He is the founder of space physiology and the initiator of the introduction of radio electronics, cybernetics, and mathematics methods into physiological research. E. A. Asratyan created a doctrine about the mechanisms of compensation for impaired functions. He is the author of a number of fundamental works developing the main provisions of the teachings of I. P. Pavlov. V. N. Chernigovsky developed the scientist V. V. PARI]] study of interoreceptors (1903--19.71)

Soviet physiologists have priority in the creation of an artificial heart (A. A. Bryukhonenko), EEG recording (V. V. Pravdich-Neminekiy), the creation of such important and new areas in science as osmic physiology, labor physiology, sports physiology, and the study of physiology. logical mechanisms of adaptation, regulation and internal mechanisms for the implementation of physiological functions. These and many other studies are of primary importance for medicine.

Knowledge of vital processes occurring in various organs and canals, mechanisms for regulating life phenomena, understanding the essence of the physiological functions of the body and the processes that interact with the environment constitute the fundamental theoretical basis on which the training of the future Doctor is based. . , ■

GENERAL PHYSIOLOGY

INTRODUCTION "

: Each of the hundred trillion cells of the human body is distinguished by an extremely complex structure, the ability to self-organize and multilateral interaction with other cells. The number of processes carried out by each cell and the amount of information processed in this process far exceeds what takes place today in any large industrial plant. Nevertheless, the cell is only one of the relatively... elementary subsystems in the complex hierarchy of systems that form a living organism.

: All these systems are highly ordered. The normal functional structure of any of them and the normal existence of each element; systems (including each cell) are possible due to the continuous exchange of information between elements (and between cells).

The exchange of information occurs through direct (contact) interaction between cells, as a result of the transfer of substances with tissue fluid, lymph! and blood (humoral connection - from the Latin humor - liquid), as well as during the transfer of bioelectric potentials from cell to cell, which is the fastest way to transmit information in the body. Multicellular organisms have developed a special system that provides perception, transmission, storage, processing and reproduction of information encoded in electrical signals. This is the nervous system that has reached its highest development in humans. To understand nature bioelectrically; phenomena, i.e., signals with the help of which the nervous system transmits information, it is necessary first of all to consider some aspects of the general physiology] of the so-called excitable tissues which include nervous, muscle and glandular tissue:

Chapter 2

PHYSIOLOGY OF EXCITABLE TISSUE

All living cells have irritability, i.e. ability under. influence!" certain factors of the external or internal environment," the so-called irritants transition from a state of physiological rest to a state of activity. However, ter min "excitable cells" They are used only in relation to nerve, muscle and secretory cells that are capable of generating specialized forms of electrical potential oscillations in response to the action of a stimulus. ■ 1

The first data on the existence of bioelectric phenomena (“animal electricity”) were obtained in the third quarter of the 18th century. when studying the nature of the electric discharge, we inflict it on some fish during Defense and Attack. The long-term scientific dispute (1791 - 1797) between the physiologist L. Galvani and the physicist A. Volta about the nature of “animal electricity” ended with two major discoveries: the facts were established , indicating the presence of electric potentials in nervous and muscle tissues, and a new way of producing electric current using dissimilar metals was discovered - a galvanic element (“voltage column”) was created. However, the first direct measurements of potentials in living tissues became possible only after the invention of the genius of galvanometers A systematic study of potentials in muscles and nerves in a state of rest and excitation was begun by Dubois-Reymond (1848).Further advances in the study of bioelectrical phenomena were closely related to the improvement of the technology for recording fast "sipping electrical potentials (string, loop and cathode oscilloscopes) and methods - ix removal from single excitable cells. A qualitatively new stage in the study of electrical phenomena in living tissues - the 40-50s of our century. -With the help of intracellular microelectro-"s, it was possible to directly record the electrical potentials of cell membranes. Advances in electronics: made it possible to develop methods for studying ionic currents flowing through the membrane when the membrane potential changes or when biologically active compounds act on membrane receptors., B In recent years, a method has been developed that makes it possible to record young currents flowing through single ion channels.

The following main types of electrical responses of excitable cells are distinguished: jucal response; spreading action potential and those accompanying him food potentials; excitatory and inhibitory postsynaptic potentials; generator potentials etc. All these potential fluctuations are based on reversible changes in the permeability of the cell membrane for certain ions. In turn, the change in permeability is a consequence of the opening and closing of ion channels existing in the cell membrane under the influence of an active stimulus. _

The energy used in the generation of electrical potentials is stored in a resting cell in the form of concentration gradients of Na +, Ca 2+, K +, C1~ ions on both sides of the surface membrane; These gradients are created and maintained by the work of specialized molecular devices, such as called membrane ionic payuses. The latter use for their work metabolic energy released during the enzymatic breakdown of the universal cellular energy donor - adenosine triphosphoric acid (ATP).

Study of electrical potentials accompanying the processes of excitation and hysteria; in living tissues is important both for understanding the nature of these processes and for identifying the nature of disturbances in the activity of excitable cells in three different types of pathology.

In modern clinics, methods for recording the electrical potentials of the heart (electrocardiography), brain (electroencephalography) and muscles (electromyography) have become especially widespread.

RESTING POTENTIAL

The term " membrane potential"(resting potential) is usually called the transjumbranous potential difference that exists between the cytoplasm and the external solution surrounding the cell. When a cell (fiber) is in a state of physiological rest, its internal potential is negative in relation to the external one, which is conventionally taken as zero. The membrane potential varies among different cells, from -50 to -90 mV.

To measure the resting potential and trace its changes caused by something or. The first effect on the cell is using the technique of intracellular microelectrodes (Fig. 1).

The microelectrode is a micropipette, that is, a thin capillary extended from a glass tube. The diameter of its tip is about 0.5 microns. The micropipette is filled with a saline solution, usually 3 M KS1, a metal electrode (chlorinated silver wire) is immersed in it and connected to an electrical measuring device - an oscilloscope equipped with a direct current amplifier.

The microelectrode is placed over the object under study, for example, a skeletal muscle, and the loan is introduced into the cell using a micromanipulator - a device equipped with micrometer screws. An electrode of normal size is immersed in a normal saline solution, in which the tissue being examined is used.

As soon as the microelectrode pierces the surface membrane of the cell, the oscilloscope beam immediately deviates from its original (zero) position, detecting

thereby the existence of a potential difference. Oscilloscope

between the surface and contents of the cell. Further advancement of the microelectrode inside the protoplasm does not affect the position of the oscilloscope beam. This indicates that the potential is indeed localized on the cell membrane.

If the microelectrode is successfully inserted, the membrane tightly covers its tip and the cell retains the ability to function for several hours without showing signs of damage.

There are many factors that change the resting potential of cells: the application of electric current, changes in the ionic composition of the medium, exposure to certain toxins, disruption of oxygen supply to tissue, etc. In all cases where the internal potential decreases (becomes less negative), we speak of membrane depolarization, the opposite shift in potential (increasing the negative charge on the inner surface of the cell membrane) is called hyperpolarization.

NATURE OF RESTING POTENTIAL

Back in 1896, V. Yu. Chagovets put forward a hypothesis about the ionic mechanism of electrical potentials in living cells and made an attempt to apply the Arrhenius theory of electrolytic dissociation to explain them. In 1902, Yu. Bernstein developed the membrane-ion theory ; which was modified and experimentally substantiated by Hodgkin, Huxley and Katz (1949-1952). Currently, the latter theory enjoys universal recognition. According to this theory, the presence of electrical potentials in living cells is due to inequality in the concentration of Na +, K +, Ca 2+ and C1~ inside and outside the cell and the different permeability of the surface membrane for them.

From the data in table. Figure 1 shows that the contents of the nerve fiber are rich in K + and organic anions (which practically do not penetrate the membrane) and poor in Na + and O - .

The concentration of K4 in the cytoplasm of nerve and muscle cells is 40-50 times higher, 4eiv in the external solution, and if the membrane at rest were permeable only to these ions, then the resting potential would correspond to the equilibrium potassium potential (Ј k) calculated by Nernst formula:

Where R gas constant, F- number, Faraday, T- absolute, temperature /Co. - concentration of free potassium ions in the external solution, Ki - their concentration* in the cytoplasm.

Rice. 1. Measuring the resting potential of a muscle fiber (A) using an intracellular microelectrode (diagram).

M - microelectrode; I - indifferent electrode. The beam on the oscilloscope screen (B) shows that before the membrane was punctured by the microelectrode, the potential difference between M and I was equal to zero. At the moment of puncture (shown by the arrow), a potential difference is detected, indicating that the inner side of the membrane is charged electronegatively with respect to its outer surface.

At Ј a.,_ .97.5 mV.

Table!

	Ratio of concentrations of internal (i) and external (o) environments, mM			Equilibrium potential for different ions, mV			Measured potentials, mV
								at maximum spike
Giant cuttlefish axon
"Vkcoh squid
Frog muscle fiber
Cat motor neuron

^is. 2. The appearance of a potential difference in an artificial membrane separating solutions of K.2SO4 of different concentrations (Ci and C 2).

The membrane is selectively permeable to K+ ions (small circles) and does not allow SO ions (large circles) to pass through). 1,2 - electrodes lowered into lacTsop; 3 - electrical measuring device.

To understand how this potential arises, consider the following model experiment (Fig. 2).

Let's imagine a vessel separated by an artificial semi-permeable membrane. The pore walls of this membrane are charged electronegatively, so they allow only cations to pass through and are impermeable to anions. A saline solution containing K+ ions begins to flow into both halves of the vessel, but their concentration in the right side of the vessel is higher than in the left. As a result of this concentration gradient, K+ ions begin to diffuse from the right half of the vessel to the left, bringing there its positive charge. This leads to the fact that non-penetrating anions begin to accumulate near the membrane in the right half of the vessel. With their negative charge, they will electrostatically hold K + at the surface of the membrane in the left half of the vessel. As a result, the membrane is polarized, and a potential difference is created between its two surfaces, corresponding to the equilibrium potassium potential (Јк). " ; ,

The assumption that in a state of rest the membrane of nerve and muscle

fibers are selectively permeable to K + and that it is their diffusion that creates the resting potential has been suggested. Bernstein back in 1902 and confirmed by Hodgkin et al. in 1962 in experiments on isolated giant squid axons. The cytoplasm (axoplasm) was carefully squeezed out of a fiber with a diameter of about 1 mm, and the collapsed membrane was filled with an artificial saline solution. When the K + concentration in the solution was close to the intracellular one, a potential difference was established between the inner and outer sides of the membrane, close to the value of the normal resting potential (- 50-g- - 80 mV), and the fiber conducted impulses. With a decrease in the intracellular and an increase in the external concentration of K +, the membrane potential decreased or even changed its sign (the potential became positive if the concentration of K + in the external solution was higher than in the internal ). .

Such experiments have shown that the concentrated K + gradient is indeed the main factor determining the value of the resting potential of the nerve fiber. However, the resting membrane is permeable not only to K +, but - (albeit to a much lesser extent) and to Na +. The diffusion of these positively charged ions into the cell reduces the absolute value of the internal negative potential of the cell created by K + diffusion. Therefore, the resting potential of the fibers (--50 + - 70 mV) is less negative than the potassium equilibrium potential calculated using the Nernst formula. > : - . ". ,

C1~ ions in nerve fibers do not play a significant role in the genesis of the resting potential, since the permeability of the resting membrane to them is relatively small. In contrast, in skeletal muscle fibers, the permeability of the resting membrane for chlorine ions is comparable to potassium, and therefore diffusion of C1~~ into the cell increases the value of the resting potential. Calculated chloride equilibrium potential (Ј a)

at a ratio = - 85 mV.

Thus, the value of the cell's resting potential is determined by two main factors: a) the ratio of the concentrations of cations and anions penetrating through the resting surface membrane; b) the ratio of membrane permeabilities for these ions. ■

To quantitatively describe this law, the Goldman-Hodgkin-Katz equation is usually used:

g -3LRK- M+ PNa- Nat+ Pa- C) r M ~ W^W^CTG "

where Ј m is the rest potential, RTo, PNa, RA- membrane permeability for K + , Na + ions and, accordingly; KЈNa<ЈClo"- наружные концентрации ионов К + ,-Na + и С1~,aKit"Na.^HС1,--их, внутренние концентрации. "

It was calculated that in an isolated giant squid axon at Ј m - -50 mV there is the following relationship between the ionic permeabilities of the resting membrane:

RTo:P\,:P<а ■ 1:0.04:0.45. .i.

The equation explains many changes in the resting potential of a cell observed experimentally and in natural conditions, for example, its persistent depolarization under the influence of certain toxins that cause an increase in sodium permeability of the membrane. These toxins include plant poisons: 1 veratridine, aconitine and one of the most powerful neurotoxins - ■batrachotoxin, produced by the skin glands of Colombian frogs.

Membrane depolarization, as follows from the equation, can occur even if P a remains unchanged if the external concentration of K + ions is increased (i.e., the Co/K ratio is increased). This change in resting potential is by no means just a laboratory phenomenon. The fact is that the concentration of K + "in the intercellular fluid increases noticeably during the activation of nerve and muscle cells, accompanied by an increase in P k. The concentration of K + in the intercellular fluid increases especially significantly during disturbances of the blood supply (ischemia) of tissues, for example, myocardial ischemia. Occurs during In this case, depolarization of the membrane leads to the cessation of the generation of action potentials, i.e., disruption of the normal electrical activity of cells.

ROLE OF METABOLISM IN THE GENESIS AND MAINTENANCE OF RESTING POTENTIAL (SODIUM MEMBRANE PUMP)

Despite the fact that the fluxes of Na + and K + through the membrane at rest are small, the difference in the concentrations of these ions inside and outside the cell should eventually level out if there were no special molecular device in the cell membrane - the “sodium pump” , which ensures the removal (“pumping out”) of Na+ penetrating into it from the cytoplasm and the introduction (“pumping”) of K+ into the cytoplasm. The sodium pump moves Na+ and K+ against their concentration gradients, i.e., it does a certain amount of work. The direct source of energy for this work is an energy-rich (macroergic) compound - adenosine triphosphoric acid (ATP), which is a universal source of energy for living cells. The breakdown of ATP is carried out by protein macromolecules - the enzyme adenosine triphosphatase (ATPase), localized in the surface membrane of the cell. The energy released during the splitting of one ATP molecule ensures the removal of three K "a" 1 " ions from the cell in exchange for two K + ions entering the cell from the outside. .

Inhibition of ATPase activity caused by certain chemical compounds (for example, the cardiac glycoside ouabain) disrupts the pump, causing the cell to lose K + and become enriched in Na + . The same result is achieved by inhibition of oxidative and glycolytic processes in the cell, which ensure the synthesis of ATP. In experiments, this is achieved with the help of poisons that inhibit these processes. In conditions where the blood supply to tissues is impaired and tissue respiration is weakened, the operation of the electrogenic pump is inhibited and, as a consequence, K+ accumulates in the intercellular gaps and membrane depolarization occurs.

The role of ATP in the mechanism of active Na + transport was directly proven in experiments on giant squid nerve fibers. It was found that by introducing ATP into the fiber, it is possible to temporarily restore the functioning of the sodium pump, impaired by the inhibitor of respiratory enzymes cyanide. \

Initially, it was believed that the sodium pump was electrically neutral, i.e., the number of exchanged Na + and K + ions was equal. Later, it turned out that for every three Na + ions removed from the cell, only two K + ions enter the cell. This means that the pump is electrogenic: it creates a potential difference on the membrane that adds up to the resting potential. -

This contribution of the sodium pump to the normal value of the resting potential is not the same in different cells: “it appears to be insignificant in squid nerve fibers, but is significant for the resting potential (about 25% of the total value) in giant neurons of mollusks, smooth muscles.

Thus, in the formation of the resting potential, the sodium pump plays a dual role: -1) creates and maintains a transmembrane concentration gradient of Na + and K +; 2) generates a potential difference that is summed with the potential created by the diffusion of JK + along the concentration gradient.

ACTION POTENTIAL

Action potential is a rapid fluctuation in membrane potential that occurs when nerve, muscle, and some other cells are excited. It is based on changes in the ionic permeability of the membrane. The amplitudes of the nature of temporary changes in the action potential depend little on the strength of the stimulus that causes it; it is only important that this strength is not less than a certain critical value, which is called the threshold of irritation. Having arisen at the site of irritation, the action potential spreads along the nerve or muscle fiber without changing its amplitude. The presence of a threshold and the independence of the amplitude of the action potential from the strength of the stimulus that caused it are called the “all or nothing” law.

L L P IIAND I J 1 III I I I NL M

A LL

Rice. 3. Skeletal muscle fiber action potential recorded using intracellular. microelectrode.

a - depolarization phase, b - rpolarization phase, c - trace depolarization phase (negative trace potential)\ The moment of application of irritation is shown by an arrow.

Rice. 4. Action potential of the squid giant axon. retracted using an intracellular electrode [Hodgkin A., 1965]. , ■ -

Displayed vertically are the values ​​of “the potential of the intracellular electrode relative to its potential in the external solution (in millivolts); a - trace positive potential; b - time stamp - 500 oscillations per 1 s."

Under natural conditions, action potentials are generated in nerve fibers when receptors are stimulated or nerve cells are excited. The propagation of action potentials along nerve fibers ensures the transmission of information in the nervous system. Having reached the nerve endings, action potentials cause the secretion of chemicals (transmitters) that provide signal transmission to the muscle or nerve cells. In muscle cells, action potentials initiate a chain of processes that cause contraction. Ions that penetrate the cytoplasm during the generation of action potentials have a regulatory effect on cell metabolism and, in particular, on the processes of synthesis of proteins that make up ion channels and ion pumps.

To record action potentials, extra- or intracellular electrodes are used. childbirth. In extracellular abduction, the electrodes are applied to the outer surface of the fiber (cell). This makes it possible to discover that the surface of the excited area for a very short time (in a nerve fiber for a thousandth of a second) becomes negatively charged in relation to the neighboring resting area.

The use of intracellular microelectrodes allows quantitative characterization of membrane potential changes during the rising and falling phases of the action potential. It was found that during the ascending phase ( depolarization phase) What happens is not just the disappearance of the resting potential (as was originally assumed), but a potential difference of the opposite sign occurs: the internal contents of the cell become positively charged in relation to the external environment, in other words, reversal of the membrane potential. During the descending phase (repolarization phase), the membrane potential returns to its original value. Figures 3 and 4 show examples of recordings of action potentials in frog skeletal muscle fiber and squid giant axon. It can be seen that at the moment of reaching the top (peak) the membrane potential is +30 + +40 mV and the peak oscillation is accompanied by long-term trace changes in the membrane potential, after which the membrane potential is established at the initial level. The duration of the action potential peak varies in different nerve and skeletal muscle fibers.

lasts from 0.5 to 3 ms, and the repolarization phase is longer than the depolarization phase. The duration of the action potential, especially the repolarization phase, is closely dependent on temperature: when cooled by 10 ° C, the duration of the peak increases approximately 3 times. -

The changes in membrane potential following the peak of the action potential are called trace potentials. "X

There are two types of trace potentials - subsequent depolarization And subsequent hyperpolarization. The amplitude of trace potentials usually does not exceed several millivolts (5-10% of the peak height), and the duration of iX 1 for various fibers ranges from several milliseconds to tens and hundreds of seconds. ",

The dependence of the peak action potential and the subsequent depolarization can be considered using the example of the electrical response of a skeletal muscle fiber. From the record shown in Fig. 3, it is clear that the descending phase of the action potential (repolarization phase) is divided into two unequal parts. Initially, the potential drop occurs rapidly then slows down greatly. This slow component of the descending phase of the action potential is called trail depolarization.■ , .

An example of the trace membrane hyperpolarization accompanying the peak of an action potential in a single (isolated) squid giant nerve fiber is shown in Fig. 4. In this case, the descending phase of the action potential directly passes into the phase of trace hyperpolarization, the amplitude of which in this case reaches 15.mV. Trace hyperpolarization is characteristic of many non-pulp nerve fibers of cold-blooded and warm-blooded animals. In myelinated nerve fibers, trace potentials are more complex. A trace depolarization can turn into a trace hyperpolarization, then sometimes a new depolarization occurs, only after which the resting potential is completely restored. Trace potentials, to a much greater extent than peaks of action potentials, are sensitive to changes in the initial resting potential, ionic composition of the environment, oxygen supply to the fiber, etc.

A characteristic feature of trace potentials is their ability to change during the process of rhythmic impulses (Fig. 5). - . .

IONIC MECHANISM OF POTENTIAL APPEARANCE ACTIONS

The action potential is based on changes in the ionic permeability of the cell membrane that develop sequentially over time.

As noted, at rest the permeability of the membrane to potassium exceeds its permeability to sodium. As a result, the flow of K+ from the cytoplasm into the external solution exceeds the oppositely directed flow of Na+. Therefore, the outer side of the membrane at rest has a positive potential relative to the inner one.

Rice; 5. Summation of trace potentials in the phrenic nerve of a cat during its short-term irritation with rhythmic impulses.;

The ascending part of the action potential is not visible. Recordings begin with negative trace potentials (a), turning into positive potentials (b). The upper curve is the response to a single stimulation. With an increase in the stimulation frequency (from 10 to 250 per 1 s), the trace positive potential (trace hyperpolarization) increases sharply.

When an irritant acts on the cell, the permeability of the “membrane for Na” 1 increases sharply and ultimately becomes approximately 20 times greater than the permeability for K + - Therefore, the flow of Na + from the external solution into the cytoplasm begins to exceed

outward potassium current. This leads to a change in the sign (reversion) of the membrane potential: the internal contents of the cell become positively charged relative to its outer surface. This change in membrane potential corresponds to the ascending phase of the action potential (depolarization phase).

The increase in membrane permeability to Na + lasts only for a very short time. Following this, the permeability of the membrane for Na + decreases again, and for K + increases. \

The process leading to a decrease in the previously increased sodium permeability of the membrane is called sodium inactivation. As a result of inactivation, the flow of Na + into the cytoplasm is sharply weakened. An increase in potassium permeability causes an increase in the flow of K + from the cytoplasm into the external solution. As a result of these two processes, membrane repolarization occurs: the internal contents of the cell again acquire a negative charge in relation to the external solution. This change potential corresponds to the descending phase of the action potential (repolarization phase).

One of the important arguments in favor of the sodium theory of the origin of action potentials was the fact of the close dependence of its amplitude on the concentration of Na" 1 " in the external solution. Experiments on giant nerve fibers perfused from the inside with saline solutions provided direct confirmation of the correctness of the sodium theory. It has been established that when the axoplasm is replaced with a saline solution rich in K+, the fiber membrane not only maintains the normal resting potential, but for a long time retains the ability to generate hundreds of thousands of action potentials of normal amplitude. If “K4” in the intracellular solution is partially replaced with Na + and thereby reduces the concentration gradient of Na + between the external environment and the internal solution, the amplitude of the action potential decreases sharply. When K+ is completely replaced by Na+, the fiber loses its ability to generate action potentials. \

These experiments leave no doubt that the surface membrane is indeed the site of potential occurrence both at rest and during excitation. It becomes obvious that the difference in concentrations of Na + and K + inside and outside the fiber is the source of the electromotive force that causes the occurrence of the resting potential and the action potential.

In Fig. Figure 6 shows changes in membrane sodium and potassium permeability during action potential generation in the squid giant axon. Similar relationships occur in other nerve fibers, the bodies of nerve cells, as well as in the skeletal muscle fibers of vertebrate animals. In the skeletal muscles of crustaceans and smooth muscles of vertebrates, Ca 2+ ions play a leading role in the genesis of the ascending phase of the action potential. In myocardial cells, the initial rise in the action potential is associated with an increase in membrane permeability for Na +, and the plateau of the action potential is due to an increase in membrane permeability for Ca 2+ ions.

ABOUT THE NATURE OF IONIC PERMEABILITY OF THE MEMBRANE. ION CHANNELS

■ _ Time, ms

Rice. 6: Time course of changes in sodium (g^a) and potassium (g k) membrane permeability of the squid giant axon during the generation of an action potential (V).

The considered changes in the ionic permeability of the membrane during the generation of an action potential are based on the processes of opening and closing of specialized ion channels in the membrane, which have two important properties: 1) selectivity in relation to certain ions; 2) electrically excite

capacity, i.e. the ability to open and close in response to changes in membrane potential. The process of opening and closing a channel is probabilistic in nature (the membrane potential only determines the probability of the channel being in an open or closed state). "

Like ion pumps, ion channels are formed by protein macromolecules that penetrate the lipid bilayer of the membrane. The chemical structure of these macromolecules has not yet been deciphered, so ideas about the functional organization of channels are still constructed mainly indirectly - based on the analysis of data obtained from studies of electrical phenomena in membranes and the influence of various chemical agents (toxins, enzymes, drugs, etc.) on the channels .). It is generally accepted that the ion channel consists of the transport system itself and the so-called gating mechanism (“gate”), controlled by the electric field of the membrane. The “gate” can be in two positions: they are completely closed or completely open, therefore the conductivity of a single open channel is a constant value. The total conductivity of the membrane for a particular ion is determined by the number of simultaneously open channels permeable to a given ion. ■ ~

This position can be written as follows:

gr. ■ /V-“7,”

Where gi- total membrane permeability for intracellular ions; N■-total number of corresponding ion channels (in a given section of the membrane); A- share of open channels; y - conductivity of a single channel.

According to their selectivity, electrically excitable ion channels of nerve and muscle cells are divided into sodium, potassium, calcium, and chloride. This selectivity is not absolute: the name of the channel indicates only the ion for which the given channel is most permeable.

Through open channels, ions move along concentration and electrical gradients. These ion flows lead to changes in membrane potential/which in turn changes the average number of open channels and, accordingly, the magnitude of ionic currents, etc. Such a circular connection is important for the generation of an action potential, but. it makes it impossible to quantify the dependence of ionic conductivity on the value of the generated potential. To study this dependence, the “potential fixation method” is used. The essence of this method is to forcibly maintain the membrane potential at any given level. Thus, by applying a current to the membrane equal in magnitude, but opposite in sign to the ionic current passing through open channels, and measuring this current at different Potentials, researchers are able to trace the dependence of the potential on the ionic conductivity of the membrane.

Internal potential

a, - solid lines show permeability during long-term depolarization, and dotted lines - during re-polarization of the membrane through -0\B and 6.3 m"s; "b"> - dependence of the peak value of sodium (g^J and the steady-state level of potassium. vry (g K) permeability o*t;membrane potential. ,

Rice. 8. Schematic representation of an electrically excitable sodium channel.

Channel (1) is formed by a macromolecule of protein 2), the narrowed part of which corresponds to a “selective filter”. The channel has activation (w) and inactivation (h) “gates”, which are controlled by the electric field of the membrane. At the resting potential (a), the most probable position is “closed” for activation gates and the “open” position for inactivation gates. Depolarization of the membrane (b) leads to the rapid opening of the t-“gate” and the slow closing of the “11-gate”, therefore, at the initial moment of depolarization, both pairs of “gates” are open and ions can move through the channel in accordance with their concentration and electrical gradients With continued depolarization (ii) the activation “gate” closes and the capal enters a state of inactivation.

branes. In order to isolate from the total ionic current flowing through the membrane its components corresponding to ion flows, for example, through sodium channels, chemical agents are used that specifically block all other channels. Proceed accordingly when measuring potassium or calcium currents.

In Fig. Figure 7 shows changes in sodium (gua) and calirva (Kk) permeability of the nerve fiber membrane during fixed depolarization. How. noted, the magnitude and gK reflect the number of simultaneously open sodium or potassium channels. As can be seen, g Na quickly, in a fraction of a millisecond, reached a maximum, and then slowly began to decrease to the initial level. After depolarization is complete, the ability of sodium channels to reopen is gradually restored over tens of milliseconds.

Action potential

Rice. 9. State of sodium and potassium channels in different phases of action potentials (diagram). Explanation in the text.

To explain this behavior of sodium channels, it has been suggested that there are two types of “gates” in each channel - fast activation and slow inactivation. As the name suggests, the initial rise in Na is associated with the opening of the activation gate (the “activation process”), and the subsequent fall during ongoing membrane depolarization is associated with the closing of the inactivation gate (the “inactivation process”).

In Fig. 8, 9 schematically depict the organization of the sodium channel, facilitating the understanding of its functions. The channel has an outer and inner embroidered region (“mouth”) and a short narrowed section, the so-called selective filter, in which cations are “selected” according to their size and properties. Judging by the size of the largest cation that penetrates through the sodium channel, the filter opening is no less than 0.3-0.5 nm. When passing through the filter, Na+ ions lose part of their hydration shell. Activation (t) and inactivation (/g) “voro”

"ta" are located in the region of the inner end of the sodium channel, and the "gate" is facing towards the cytoplasm. This conclusion was reached based on the fact that the application of some proteolytic* enzymes (pronase) to the inner side of the membrane leads to the elimination of sodium inactivation (destroys /g-“gate”), . "

At rest "gate" T closed, while the "gate" h open. During depolarization at the initial moment of the “gate” tmh open - the channel is in a conducting state. Then the inactivation gate closes and the channel is inactivated. After the end of depolarization, the “gate” h slowly opens, and the “gate” t quickly closes and the channel returns to its original resting state. . , U

A specific sodium channel blocker is tetrodotoxin, a compound synthesized in the tissues of some fish species. and salamanders. This compound enters the outer mouth of the channel, binds to some as yet unidentified chemical groups and “clogs” the channel. Using radioactively labeled tetrodotoxin, the density of sodium channels in the membrane was calculated. In different cells, this density varies from tens to tens of thousands of sodium channels per square micron of membrane, ■ "

The functional organization of potassium channels is similar to that of sodium channels, the only differences being their selectivity and the kinetics of activation and inactivation processes. The selectivity of potassium channels is higher than the selectivity of sodium channels: for Na + potassium channels are practically impermeable; the diameter of their selective filter is about 0.3 nm. Activation of potassium channels has approximately an order of magnitude slower kinetics than activation of sodium channels (see Fig. 7). During 10 ms depolarization gK does not show a tendency towards inactivation: potassium “inactivation develops only with multi-second depolarization of the membrane.

It should be emphasized that such relationships between the processes of activation and inactivation

potassium channels are characteristic only of nerve fibers. In the membrane of many nerve and muscle cells there are potassium channels that are relatively quickly inactivated. Rapidly activated potassium channels have also been discovered. Finally, there are potassium channels that are activated not by the membrane potential, but by intracellular Ca 2+,

Potassium channels are blocked by the organic cation tetraethylammonium, as well as aminopyridines. h

Calcium channels are characterized by slow kinetics of activation (milliseconds) and inactivation (tens and hundreds of milliseconds). Their selectivity is determined by the presence in the area of ​​the outer mouth of some chemical groups that have an increased affinity for divalent cations: Ca 2+ binds to these groups and only after that passes into the channel cavity. For some divalent cations, the affinity for these groups is so great that when they bind to them, they block the movement of Ca + through the channel. This is how calcium channels work

It can also be blocked by certain organic compounds (verapamil, nifedipine) used in clinical practice to suppress increased electrical activity of smooth muscles. h

A characteristic feature of calcium channels is their dependence on metabolism and, in particular, on cyclic nucleotides (cAMP and cGMP), which regulate the processes of phosphorylation and dephosphorylation of calcium channel proteins. "

The rate of activation and inactivation of all ion channels increases with increasing membrane depolarization; Accordingly, the number of simultaneously open channels increases to a certain limiting value.

MECHANISMS OF CHANGES IN IONIC CONDUCTIVITY DURING ACTION POTENTIAL GENERATION

It is known that the ascending phase of the action potential is associated with an increase in sodium permeability. The promotion process develops as follows.

In response to the initial stimulus-induced membrane depolarization, only a small number of sodium channels open. Their opening, however, results in a flow of Na + ions entering the cell (incoming sodium current), which increases the initial depolarization. This leads to the opening of new sodium channels, i.e., to a further increase in gNa, respectively, of the incoming sodium current, and consequently, to further “depolarization of the membrane, which, in turn, causes an even greater increase in gNa, etc. Such a circular” the avalanche process is called regenerative (i.e. self-renewing) depolarization. Schematically it can be depicted as follows:

->- Membrane depolarization

Stimulus

G 1

Incoming. Increased sodium -"-sodium permeability current

Theoretically, regenerative depolarization should end with an increase in the internal potential of the cell to the value of the equilibrium Nernst potential for Ka ions:

where Na^" is external, aNa^ is internal: the concentration of Na + ions, "With the observed ratio of 10 Ј Na = +55 mV.

This value is the limit for the action potential. In reality, however, the peak potential never reaches the value Ј Na,. firstly, because the membrane at the moment of the peak of the action potential is permeable not only to Na + ions, but also to K + ions (to a much lesser extent). Secondly, the rise of the action potential to the value Em a is counteracted by restoration processes leading to the restoration of the original polarization (membrane repolarization). v

Such processes are a decrease in value gNll and raising the level

The decrease in Na is due to the fact that the activation of sodium channels during depolarization is replaced by their inactivation; this leads to a rapid decrease in the number of open sodium channels. At the same time, under the influence of depolarization, slow activation of potassium channels begins, causing an increase in the g K value. A consequence of the increase gK is an increase in the flow of K + ions leaving the cell (outgoing potassium current). .

Under conditions of decrease associated with inactivation of sodium channels, the outgoing current of K + ions leads to repolarization of the membrane or even to its temporary (“trace”) hyperpolarization, as occurs, for example, in the giant axon of the squid (see, Fig. 4 ).

Membrane repolarization in turn leads to the closure of potassium channels^ and, consequently, to a weakening of the outward potassium current. At the same time, under the influence of repolarization, sodium inactivation is slowly eliminated: the inactivation gate opens and sodium channels return to a resting state.

In Fig. Figure 9 schematically shows the state of sodium and potassium channels during various phases of action potential development.

All agents that block sodium channels (tetrodotoxin, local anesthetics and many other drugs) reduce the slope and amplitude of the action potential, and to a greater extent, the higher the concentration of these substances.

ACTIVATION OF SODIUM-POTASSIUM PUMP "

WHEN EXCITED

The occurrence of a series of impulses in a nerve or muscle fiber is accompanied by an enrichment of protoplasm in Na + and loss of K +. For a giant squid axon with a diameter of 0.5 mm, it is calculated that during a single nerve impulse, through each square micron of membrane, about 20 OONA + enters the protoplasm and the same amount of K + leaves the fiber. As a result, with each impulse, the axon loses about one millionth of the total potassium content . Although these losses are very insignificant, with the rhythmic repetition of pulses, when added up, they should lead to more or less noticeable changes in concentration gradients.

Such concentration shifts should develop especially quickly in thin nerve and muscle fibers and small nerve cells, which have a small volume of cytoplasm relative to the surface. This, however, is counteracted by the sodium pump, the activity of which increases with increasing intracellular concentration of Na + ions.

Increased pump activity is accompanied by a significant increase in the intensity of metabolic processes that supply energy for the active transfer of Na + and K + ions across the membrane. This is an increase in the processes of breakdown and synthesis of ATP and creatine phosphate, an increase in cell oxygen consumption, an increase in heat production, etc.

Thanks to the operation of the pump, the inequality of concentrations of Na + and K + on both sides of the membrane, which was disrupted during excitation, is completely restored. It should, however, be emphasized that the rate of removal of Na + from the cytoplasm using a pump is relatively low: it is approximately 200 times lower than the rate of movement of these ions through the membrane along the concentration gradient.

Metabolism Inside: Not enough. K a lot

Thus, in a living cell there are two systems for the movement of ions through the membrane (Fig. 10). One of them is carried out along an ion concentration gradient and does not require energy, therefore it is called passive ion transport. It is responsible for the occurrence of the resting potential and the action potential and ultimately leads to equalization of the concentration of ions on both sides of the cell membrane: The second type of ion movement through the membrane, carried out against the concentration gradient, consists of “pumping” sodium ions from the cytoplasm and “pumping” potassium ions into the cell. This type of ion transport is possible only if metabolic energy is consumed. He is called active ion transport. It is responsible for maintaining a constant difference in ion concentrations between the cytoplasm and the fluid surrounding the cell. Active transport is the result of the work of the sodium pump, thanks to which the initial difference in ion concentrations, which is disrupted with each outbreak of excitation, is restored.

Rice. 10. Two systems of ion transport through the membrane.

On the right is the movement of Na + and Kn ions through ion channels during excitation in accordance with concentration and electrical gradients. On the left is active transport of ions against the concentration gradient due to metabolic energy (“sodium pump”). Active transport ensures the maintenance and restoration of ion gradients that change during pulse activity. The dotted line indicates that part of the outflow of Na + that does not disappear when K + ions are removed from the external solution [Hodgkin A., 1965]. ..

MECHANISM OF CELL (FIBER) IRRITATION BY ELECTRIC CURRENT

Under natural conditions, the generation of an action potential is caused by so-called local currents that arise between excited (depolarized) and resting sections of the cell membrane. Therefore, electric current is considered as an adequate stimulus for excitable membranes and is successfully used in experiments to study the patterns of the occurrence of action potentials.

The minimum current strength necessary and sufficient to initiate an action potential is called threshold, Accordingly, stimuli of greater and lesser strength are designated subthreshold and suprathreshold. The threshold current strength (threshold current), within certain limits, is inversely related to the duration of its action. There is also a certain minimum slope for the increase in current strength,<(которой последний утрачивает способность вызывать потенциал действия.

There are two ways to apply current to tissues to measure the threshold of irritation and, therefore, to determine their excitability. In the first method - extracellular - both electrodes are placed on the surface of the irritated tissue. It is conventionally assumed that the applied current enters the tissue in the anode region and exits in the cathode region (Fig. I). The disadvantage of this method of measuring the threshold is the significant branching of the current: only part of it flows through cell membranes, while part branches off into the intercellular gaps. As a result, during irritation it is necessary to apply a current of much greater strength than is necessary to cause excitation. : " -

In the second method of supplying current to cells - intracellular -, a microelectrode is inserted into the cell, and a regular electrode is applied to the surface of the tissue (Fig> 12). In this case, all the current passes through the cell membrane, which allows you to accurately determine the smallest current required to cause an action potential. With this stimulation method, potentials are removed using a second intracellular microelectrode.

The threshold current required to cause excitation of various cells with an intracellular stimulating electrode is 10~ 7 - 10 -9 A.

In laboratory conditions and during some clinical studies, electrical stimuli of various shapes are used to irritate nerves and muscles: rectangular, sinusoidal, linearly and exponentially increasing, induction shocks, capacitor discharges, etc., -

The mechanism of the irritating effect of current for all types of stimuli is in principle the same, but in its most distinct form it is revealed when using direct current.

Rice. 11, Branching of current in tissue during stimulation through external (extracellular) electrodes (diagram). :

Oscilloscope

Stimulus-1 "-fG Amplifier l * torus T7 post, tone

Rice. 12. Irritation and removal of potentials through intracellular microelectrodes. Explanation in the text.

The muscle fibers are shaded; between them there are intercellular gaps.

2 Human physiology

EFFECT OF DC CURRENT ON EXCITABLE TISSUE

Polar law of irritation

When a nerve or muscle is irritated by direct current, excitation occurs at the moment of closure of the direct current only under the cathode, and at the moment of opening - only under the anode. These facts are united under the name of the polar law of irritation, discovered by Pfluger in 1859. The polar law is proven by the following experiments. The area of ​​the nerve under one of the electrodes is killed, and the second electrode is installed on the undamaged area. If it comes into contact with an undamaged area. cathode, excitation, occurs at the moment the current closes; if the cathode is poured into a damaged area, and the anode into an undamaged area, excitation occurs only when the current is opened. The threshold of irritation during opening, when excitation occurs under the anode, is significantly lower than during closure, when excitation occurs under the cathode.

The study of the mechanism of the polar action of electric current became possible only after the described method of simultaneous introduction of two microelectrodes into the aunts was developed: one for stimulation, the other for removing potentials. It was found that an action potential occurs only if the cathode is outside and the anode is inside the cell. With the reverse arrangement of the tolis, i.e., the outer anode and the inner cathode, excitation when the current is closed, no matter how strong it is. 1 "" g

Passing through a nervous or. muscle fiber electrical current primarily causes changes in membrane potential^.

In the area where the anode is applied to the surface of the tissue, the positive potential on the outer side of the membrane increases, i.e., hyperpolarization occurs, and in the case when the cathode is applied to the surface, the positive potential on the outer side of the membrane decreases, and depolarization occurs. . ,.

In Fig. 13a shows that both when the current is closed and when the current is opened, changes in the membrane potential of the nerve fiber do not arise or disappear instantly, but develop smoothly over time. " "

This is explained by the fact that the surface membrane of a living cell has the properties of a capacitor. The outer and inner surfaces of the membrane serve as the plates of this “tissue capacitor”, and the dielectric is a layer of lipids with significant resistance. Due to the presence of channels in the membrane through which ions can pass, the resistance of this layer is not infinite, as in an ideal capacitor. Therefore, the surface membrane of a cell is usually likened to a capacitor with a resistance connected in parallel, through which leakage of charges can occur (Fig. 13, a).

The time course of changes in the membrane potential when the current is turned on and off (Fig. 13b) depends on the capacitance C and the membrane resistance R. The smaller the product DC is the time constant of the membrane, the faster the potential increases at a given current strength and, conversely, the greater The RC value corresponds to a lower rate of potential increase.

Changes in membrane potential occur not only directly at the points where direct current is applied to the cathode and anode to the nerve fiber, but also at some distance from the poles, with the difference, however, that their magnitude gradually decreases with distance from the cathode and anode. This is explained by the so-called cable properties of nerve and muscle fibers. Electrically, a homogeneous nerve fiber is a cable, i.e. a core with low resistivity (axoplasm), covered with insulation (membrane), and placed in a well-conducting medium. An equivalent cable diagram is shown in Fig. 13, b. When When a constant current is passed through a certain point of the fiber for a long time, a stationary state is observed in which the current density and, consequently, the change in the membrane potential are maximum at the point of application of the current (i.e., directly under the cathode and anode); With distance from the poles, the current density and potential changes on the membrane decrease exponentially along the length of the fiber. Since the changes in the membrane potential under consideration, in contrast to the local, action potential response or trace potentials, are not associated with changes in the ionic permeability of the membrane (i.e., the active response of the fiber), they are usually called passive,

Potential

Rice. 13. The simplest electrical circuit that reproduces the electrical properties of the membrane (a and changes in the membrane potential under the cathode and anode of direct current. subthreshold force (b).

a: C - membrane capacitance, R - resistance, E - electromotive force of the membrane at rest (potential; rest).. The average values ​​of R, C and E for a motor neuron are given, b - depolarization of the membrane (1) under the cathode and hyperpolarization (2) under the anode when a weak subthreshold current passes through the nerve fiber. . "

or " electrotonic changes in membrane potential. In their pure form, the latter can be registered under conditions of complete blockade of ion channels by chemical agents. They differ cat- And anelectrotonic potential changes developing in the area of ​​application of the cathode and anode, respectively, of direct current. -

Critical level of depolarization

- \ Registration of changes in membrane potential during intracellular stimulation of a nerve or muscle fiber showed that the action potential arises in. the moment when membrane depolarization reaches a critical level. This critical level of depolarization does not depend on the nature of the stimulus applied, the distance between the electrodes, etc., but is determined solely by the properties of the membrane itself.

In Fig. Figure 14 schematically shows changes in the membrane potential of a nerve fiber under the influence of long and short stimuli of varying strength. In all cases, the action potential occurs when the membrane potential reaches a critical value. The speed at which it happens

membrane depolarization, all other things being equal 4

External side

Inner side

conditions depends on the strength of the irritating current. With a weak current, depolarization develops slowly, therefore. For an action potential to occur, the stimulus must be of greater duration. If the irritating current increases, the rate of development of depolarization increases. Accordingly, the minimum time required for excitation to occur decreases. The faster the membrane depolarization develops, the shorter the minimum time required to generate a potential by actions in reverse.

Local response

In the mechanism of critical membrane depolarization, along with passive ones, active subthreshold changes in the membrane potential, manifested in the form of the so-called local response, play a significant role.

Rice. 14. Change in membrane potential to a critical level of membrane depolarization under the action of an irritating current of varying strength and duration.

The critical level is shown with a dotted line. Below are irritating stimuli, under the influence of which responses A, B and C were obtained.

e is. 15. Local response of the nerve fiber.

B, C - changes in the membrane potential of the 1st nerve fiber caused by the action of a subthreshold current of short duration. On curves B and 3, active subthreshold depolarization will also be added to the passive depolarization of the membrane in the form of a local response. The local response is separated from the passive ones changes in potential with a dotted line. At a threshold current strength (G), the local response develops into an action potential (its tip is not shown in the figure).

person 1

UK1 5L4 2

gr. ■ /V-“7,” 40

CONDUCTION OF NERVE IMPULSE AND NEUROMUSCULAR TRANSMISSION 113

INTRODUCTION 147

GENERAL PHYSIOLOGY OF THE CENTRAL NERVOUS SYSTEM 150

private physiology 197

central nervous system 197

NERVOUS REGULATION OF AUTONOMIC FUNCTIONS 285

hormonal regulation of physiological functions 306

“Human Physiology Edited by Corresponding Member. Academy of Medical Sciences of the USSR G.I. KOSITSKY THIRD EDITION, REVISED AND ADDED Approved by the Main Directorate of Educational Institutions of the Ministry of Health of the USSR as a textbook for...”

-- [ Page 1 ] --

EDUCATIONAL LITERATURE

For medical students

Physiology

person

Edited by

member-corr. Academy of Medical Sciences of the USSR G. I. KOSITSKY

THIRD EDITION, REVISED

AND EXTRA

Approved by the Main Directorate of Educational Institutions of the USSR Ministry of Health as a textbook

for medical students

Moscow “Medicine” 1985

E. B. BABSKY V. D. GLEBOVSKY, A. B. KOGAN, G. F. KOROTKO, G. I. KOSITSKY, V. M. POKROVSKY, Y. V. NATOCHIN, V. P.

SKIPETROV, B. I. KHODOROV, A. I. SHAPOVALOV, I. ​​A. SHEVELEV Reviewer I. D. Boyenko, prof., head. Department of Normal Physiology, Voronezh Medical Institute named after. N. N. Burdenko Human Physiology / Ed. G.I. Kositsky. - F50 3rd ed., revised. and additional - M.: Medicine, 1985. 544 p., ill.

In the lane: 2 r. 20 k. 15 0 000 copies.

The third edition of the textbook (the second was published in 1972) was written in accordance with the achievements of modern science. New facts and concepts are presented, new chapters are included: “Features of human higher nervous activity”, “Elements of labor physiology, mechanisms of training and adaptation”, sections covering issues of biophysics and physiological cybernetics are expanded. Nine chapters of the textbook were written anew, the rest were largely revised.

The textbook corresponds to the program approved by the USSR Ministry of Health and is intended for students of medical institutes.

2007020000-241 BBK 28. 039(01) - Medicine Publishing House,

PREFACE

12 years have passed since the previous edition of the textbook “Human Physiology”.

The responsible editor and one of the authors of the book, Academician of the Academy of Sciences of the Ukrainian SSR E.B. Babsky, according to whose manuals many generations of students studied physiology, has passed away.

Shapovalov and prof. Yu. V. Natochin (head of laboratories of the I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the USSR Academy of Sciences), prof. V.D. Glebovsky (Head of the Department of Physiology, Leningrad Pediatric Medical Institute), prof. A.B. Kogan (Head of the Department of Human and Animal Physiology and Director of the Institute of Neurocybernetics of Rostov State University), prof. G. F. Korotko (Head of the Department of Physiology, Andijan Medical Institute), prof. V.M. Pokrovsky (Head of the Department of Physiology, Kuban Medical Institute), prof. B.I. Khodorov (head of the laboratory of the A.V. Vishnevsky Institute of Surgery of the USSR Academy of Medical Sciences), prof. I. A. Shevelev (head of the laboratory of the Institute of Higher Nervous Activity and Neurophysiology of the USSR Academy of Sciences).

Over the past time, a large number of new facts, views, theories, discoveries and directions of our science have appeared. In this regard, 9 chapters in this edition had to be written anew, and the remaining 10 chapters had to be revised and supplemented. At the same time, to the extent possible, the authors tried to preserve the text of these chapters.

The new sequence of presentation of the material, as well as its combination into four main sections, is dictated by the desire to give the presentation logical harmony, consistency and, as far as possible, to avoid duplication of material.

The content of the textbook corresponds to the physiology program approved in the year. Critical comments about the project and the program itself, expressed in the resolution of the Bureau of the Department of Physiology of the USSR Academy of Sciences (1980) and at the All-Union Meeting of Heads of Physiology Departments of Medical Universities (Suzdal, 1982), were also taken into account. In accordance with the program, chapters were introduced into the textbook that were missing in the previous edition: “Features of higher nervous activity of man” and “Elements of labor physiology, mechanisms of training and adaptation,” and sections covering issues of particular biophysics and physiological cybernetics were expanded. The authors took into account that in 1983 a textbook of biophysics for students of medical institutes was published (ed.

prof. Yu.A.Vladimirov) and that the elements of biophysics and cybernetics are presented in the textbook by prof. A.N. Remizov “Medical and biological physics”.

Due to the limited volume of the textbook, it was necessary, unfortunately, to omit the chapter “History of Physiology”, as well as excursions into history in individual chapters. Chapter 1 gives only outlines of the formation and development of the main stages of our science and shows its importance for medicine.

Our colleagues provided great assistance in creating the textbook. At the All-Union Meeting in Suzdal (1982), the structure was discussed and approved, and valuable suggestions were made regarding the content of the textbook. Prof. V.P. Skipetrov revised the structure and edited the text of the 9th chapter and, in addition, wrote its sections relating to blood coagulation. Prof. V. S. Gurfinkel and R. S. Person wrote subsection 6 “Regulation of movements.” Assoc. N. M. Malyshenko presented some new materials for Chapter 8. Prof. I.D.Boenko and his staff expressed many useful comments and wishes as reviewers.

Employees of the Department of Physiology II MOLGMI named after N. I. Pirogova prof. L. A. Mipyutina associate professors I. A. Murashova, S. A. Sevastopolskaya, T. E. Kuznetsova, Ph.D. mpngush and L. M. Popova took part in the discussion of the manuscript of some chapters.

I would like to express our deep gratitude to all these comrades.

The authors are fully aware that in such a difficult task as creating a modern textbook, shortcomings are inevitable and therefore will be grateful to everyone who makes critical comments and suggestions about the textbook.

PHYSIOLOGY AND ITS IMPORTANCE

Physiology (from the Greek physis - nature and logos - teaching) is the science of the life activity of the whole organism and its individual parts: cells, tissues, organs, functional systems. Physiology seeks to reveal the mechanisms of the functions of a living organism, their connection with each other, regulation and adaptation to the external environment, origin and formation in the process of evolution and individual development of the individual.

Physiological patterns are based on data on the macro- and microscopic structure of organs and tissues, as well as on the biochemical and biophysical processes occurring in cells, organs and tissues. Physiology synthesizes specific information obtained by anatomy, histology, cytology, molecular biology, biochemistry, biophysics and other sciences, combining them into a single system of knowledge about the body.

Thus, physiology is a science that implements a systematic approach, i.e.

study of the body and all its elements as systems. The systems approach focuses the researcher primarily on revealing the integrity of the object and the mechanisms that support it, i.e. to identify diverse types of connections of a complex object and reduce them into a single theoretical picture.

The object of study of physiology is a living organism, the functioning of which as a whole is not the result of a simple mechanical interaction of its constituent parts. The integrity of the organism does not arise as a result of the influence of some supramaterial essence, which unquestioningly subjugates all the material structures of the organism. Similar interpretations of the integrity of the organism existed and still exist in the form of a limited mechanistic (metaphysical) or no less limited idealistic (vitalistic) approach to the study of life phenomena.

The errors inherent in both approaches can be overcome only by studying these problems from a dialectical-materialist position. Therefore, the patterns of activity of the organism as a whole can be understood only on the basis of a consistently scientific worldview. For its part, the study of physiological laws provides rich factual material illustrating a number of provisions of dialectical materialism. The connection between physiology and philosophy is thus two-way.

Physiology and medicine By revealing the basic mechanisms that ensure the existence of the whole organism and its interaction with the environment, physiology makes it possible to find out and study the causes, conditions and nature of disturbances in the activity of these mechanisms during illness. It helps to determine the ways and means of influencing the body, with the help of which its functions can be normalized, i.e. restore health.

Therefore, physiology is the theoretical basis of medicine; physiology and medicine are inseparable. The doctor assesses the severity of the disease by the degree of functional impairment, i.e. by the magnitude of deviation from the norm of a number of physiological functions. Currently, such deviations are measured and quantified. Functional (physiological) studies are the basis of clinical diagnosis, as well as a method for assessing the effectiveness of treatment and prognosis of diseases. Examining the patient, establishing the degree of impairment of physiological functions, the doctor sets himself the task of returning these functions to normal.

However, the importance of physiology for medicine is not limited to this. The study of the functions of various organs and systems has made it possible to simulate these functions using instruments, devices and devices created by human hands. In this way, an artificial kidney (hemodialysis machine) was constructed. Based on the study of the physiology of the heart rhythm, a device for electrical stimulation of the heart was created, which ensures normal cardiac activity and the possibility of returning to work for patients with severe heart damage. An artificial heart and heart-lung machines (heart-lung machines) have been manufactured, which make it possible to turn off the patient’s heart during a complex heart operation. There are defibrillation devices that restore normal cardiac activity in case of fatal disorders of the contractile function of the heart muscle.

Research in the field of respiratory physiology made it possible to design a device for controlled artificial respiration (“iron lungs”). Devices have been created that can be used to turn off a patient’s breathing for a long time during operations or to maintain the life of the body for years in case of damage to the respiratory center. Knowledge of the physiological laws of gas exchange and gas transport helped to create installations for hyperbaric oxygenation. It is used for fatal lesions of the blood system, as well as the respiratory and cardiovascular systems.

Based on the laws of brain physiology, techniques for a number of complex neurosurgical operations have been developed. Thus, electrodes are implanted into the cochlea of ​​a deaf person, through which electrical impulses are sent from artificial sound receivers, which to a certain extent restores hearing.

These are just a few examples of the use of the laws of physiology in the clinic, but the significance of our science goes far beyond the boundaries of just medical medicine.

The role of physiology in ensuring human life and activity in various conditions The study of physiology is necessary for scientific substantiation and creation of conditions for a healthy lifestyle that prevents diseases. Physiological laws are the basis of the scientific organization of labor in modern production. Physiology has made it possible to develop a scientific basis for various individual training regimes and sports loads that underlie modern sports achievements. And not only sports. If you need to send a person into space or lower him into the depths of the ocean, undertake an expedition to the north and south poles, reach the peaks of the Himalayas, explore the tundra, taiga, desert, place a person in conditions of extremely high or low temperatures, move him to different time zones or climatic conditions conditions, then physiology helps to justify and provide everything necessary for human life and work in such extreme conditions.

Physiology and technology Knowledge of the laws of physiology was required not only for scientific organization and increasing labor productivity. Over billions of years of evolution, nature is known to have achieved the highest perfection in the design and control of the functions of living organisms. The use in technology of principles, methods and methods operating in the body opens up new prospects for technical progress. Therefore, at the intersection of physiology and technical sciences, a new science - bionics - was born.

The successes of physiology contributed to the creation of a number of other fields of science.

DEVELOPMENT OF PHYSIOLOGICAL RESEARCH METHODS

Physiology was born as an experimental science. She obtains all data through direct research into the vital processes of animal and human organisms. The founder of experimental physiology was the famous English physician William Harvey.

“Three hundred years ago, amid the deep darkness and now difficult to imagine confusion that reigned in ideas about the activities of animal and human organisms, but illuminated by the inviolable authority of the scientific classical heritage, the physician William Harvey spied one of the most important functions of the body - blood circulation, and thereby laid the foundation a new department of precise human knowledge of animal physiology,” wrote I.P. Pavlov. However, for two centuries after the discovery of blood circulation by Harvey, the development of physiology occurred slowly. It is possible to list relatively few fundamental works of the 17th-18th centuries. This is the opening of capillaries (Malpighi), the formulation of the principle of reflex activity of the nervous system (Descartes), the measurement of blood pressure (Hels), the formulation of the law of conservation of matter (M.V. Lomonosov), the discovery of oxygen (Priestley) and the commonality of combustion and gas exchange processes ( Lavoisier), the discovery of “animal electricity”, i.e.

the ability of living tissues to generate electrical potentials (Galvani), and some other works.

Observation as a method of physiological research. The comparatively slow development of experimental physiology over the two centuries after Harvey's work is explained by the low level of production and development of natural science, as well as the difficulties of studying physiological phenomena through their usual observation. Such a methodological technique has been and remains the cause of numerous complex processes and phenomena, which is a difficult task. The difficulties created by the method of simple observation of physiological phenomena are eloquently evidenced by the words of Harvey: “The speed of cardiac motion does not make it possible to distinguish how systole and diastole occur, and therefore it is impossible to know at what moment and in which part expansion and contraction occur. Indeed, I could not distinguish systole from diastole, since in many animals the heart appears and disappears in the blink of an eye, with the speed of lightning, so it seemed to me that once there was systole and here there was diastole, and another time it was the other way around. There is difference and confusion in everything.”

Indeed, physiological processes are dynamic phenomena. They are constantly developing and changing. Therefore, it is possible to directly observe only 1-2 or, at best, 2-3 processes. However, in order to analyze them, it is necessary to establish the relationship of these phenomena with other processes that remain unnoticed with this method of research. In this regard, simple observation of physiological processes as a research method is a source of subjective errors. Usually observation allows us to establish only the qualitative side of phenomena and makes it impossible to study them quantitatively.

An important milestone in the development of experimental physiology was the invention of the kymograph and the introduction of the method of graphically recording blood pressure by the German scientist Karl Ludwig in 1843.

Graphic registration of physiological processes. The graphic recording method marked a new stage in physiology. It made it possible to obtain an objective record of the process being studied, which minimized the possibility of subjective errors. In this case, the experiment and analysis of the phenomenon under study could be carried out in two stages.

During the experiment itself, the experimenter's task was to obtain high-quality recordings - curves. The analysis of the obtained data could be carried out later, when the experimenter’s attention was no longer distracted by the experiment.

The graphic recording method made it possible to record simultaneously (synchronously) not one, but several (theoretically unlimited number) physiological processes.

Quite soon after the invention of recording blood pressure, methods for recording the contraction of the heart and muscles were proposed (Engelman), an air transmission method was introduced (Marey’s capsule), which made it possible to record, sometimes at a considerable distance from the object, a number of physiological processes in the body: respiratory movements of the chest and abdominal cavity, peristalsis and changes in the tone of the stomach, intestines, etc. A method was proposed for recording vascular tone (Mosso plethysmography), changes in volume, various internal organs - oncometry, etc.

Research of bioelectric phenomena. An extremely important direction in the development of physiology was marked by the discovery of “animal electricity”. Luigi Galvani's classic "second experiment" showed that living tissues are a source of electrical potentials capable of influencing the nerves and muscles of another organism and causing muscle contraction. Since then, for almost a century, the only indicator of potentials generated by living tissues (bioelectric potentials) was a frog neuromuscular preparation. He helped discover the potentials generated by the heart during its activity (the experience of Kölliker and Müller), as well as the need for continuous generation of electrical potentials for constant muscle contraction (the experience of “secondary tetanus” by Mateuchi). It became clear that bioelectric potentials are not random (side) phenomena in the activity of living tissues, but signals with the help of which commands are transmitted in the body to the nervous system and from it to muscles and other organs, and thus living tissues interact with each other using "electric tongue"

It was possible to understand this “language” much later, after the invention of physical devices that captured bioelectric potentials. One of the first such devices was a simple telephone. The remarkable Russian physiologist N.E. Vvedensky, using a telephone, discovered a number of the most important physiological properties of nerves and muscles. Using the phone, we were able to listen to bioelectric potentials, i.e. explore them through observation. A significant step forward was the invention of a technique for objective graphic recording of bioelectric phenomena. The Dutch physiologist Einthoven invented a string galvanometer - a device that made it possible to record on photographic paper the electrical potentials arising during the activity of the heart - an electrocardiogram (ECG). In our country, the pioneer of this method was the largest physiologist, student of I.M. Sechenov and I.P. Pavlov, A.F. Samoilov, who worked for some time in Einthoven’s laboratory in Leiden.

History has preserved interesting documents. A. F. Samoilov wrote a humorous letter in 1928:

“Dear Einthoven, I am writing a letter not to you, but to your dear and respected string galvanometer. That’s why I turn to him: Dear galvanometer, I just learned about your anniversary.

Very soon the author received a response from Einthoven, who wrote: “I exactly fulfilled your request and read the letter to the galvanometer. Undoubtedly, he listened and accepted with pleasure and joy everything that you wrote. He had no idea that he had done so much for humanity. But at the point where you say that he cannot read, he suddenly became furious... so much so that my family and I even became agitated. He shouted: What, I can’t read? This is a terrible lie. Am I not reading all the secrets of the heart? “Indeed, electrocardiography very soon moved from physiological laboratories to the clinic as a very advanced method for studying the condition of the heart, and many millions of patients today owe their lives to this method.

Samoilov A.F. Selected articles and speeches.-M.-L.: Publishing House of the USSR Academy of Sciences, 1946, p. 153.

Subsequently, the use of electronic amplifiers made it possible to create compact electrocardiographs, and telemetry methods make it possible to record ECGs from astronauts in orbit, from athletes on the track and from patients in remote areas, from where the ECG is transmitted via telephone wires to large cardiological institutions for comprehensive analysis.

Objective graphic recording of bioelectric potentials served as the basis for the most important branch of our science - electrophysiology. A major step forward was the proposal of the English physiologist Adrian to use electronic amplifiers to record bioelectric phenomena. Soviet scientist V.V. PravdichNeminsky was the first to record the biocurrents of the brain - he obtained an electroencephalogram (EEG). This method was later improved by the German scientist Berger. Currently, electroencephalography is widely used in the clinic, as well as graphic recording of electrical potentials of muscles (electromyography), nerves and other excitable tissues and organs. This made it possible to conduct a subtle assessment of the functional state of these organs and systems. For physiology itself, these methods were also of great importance: they made it possible to decipher the functional and structural mechanisms of the activity of the nervous system and other organs and tissues, and the mechanisms of regulation of physiological processes.

An important milestone in the development of electrophysiology was the invention of microelectrodes, i.e. the thinnest electrodes, the tip diameter of which is equal to fractions of a micron. These electrodes, using appropriate devices - micromanipulations, can be inserted directly into the cell and bioelectric potentials can be recorded intracellularly.

Microelectrodes made it possible to decipher the mechanisms of generation of biopotentials, i.e. processes occurring in cell membranes. Membranes are the most important formations, since through them the processes of interaction of cells in the body and individual elements of the cell with each other are carried out. The science of the functions of biological membranes—membranology—has become an important branch of physiology.

Methods of electrical stimulation of organs and tissues. A significant milestone in the development of physiology was the introduction of the method of electrical stimulation of organs and tissues.

Living organs and tissues are capable of responding to any influence: thermal, mechanical, chemical, etc., electrical stimulation, by its nature, is closest to the “natural language” with the help of which living systems exchange information. The founder of this method was the German physiologist Dubois-Reymond, who proposed his famous “sleigh apparatus” (induction coil) for dosed electrical stimulation of living tissues.

Currently, electronic stimulators are used for this, allowing one to receive electrical impulses of any shape, frequency and strength. Electrical stimulation has become an important method for studying the functions of organs and tissues. This method is widely used in the clinic. Designs of various electronic stimulators have been developed that can be implanted into the body. Electrical stimulation of the heart has become a reliable way to restore the normal rhythm and functions of this vital organ and has returned hundreds of thousands of people to work. Electrical stimulation of skeletal muscles has been successfully used, and methods of electrical stimulation of areas of the brain using implanted electrodes are being developed. The latter, using special stereotactic devices, are introduced into strictly defined nerve centers (with an accuracy of fractions of a millimeter). This method, transferred from physiology to the clinic, made it possible to cure thousands of severe neurological patients and obtain a large amount of important data on the mechanisms of the human brain (N. P. Bekhtereva). We have talked about this not only to give an idea of ​​some of the methods of physiological research, but also to illustrate the importance of physiology for the clinic.

In addition to recording electrical potentials, temperature, pressure, mechanical movements and other physical processes, as well as the results of the effects of these processes on the body, chemical methods are widely used in physiology.

Chemical methods in physiology. The language of electrical signals is not the most universal in the body. The most common is the chemical interaction of vital processes (chains of chemical processes occurring in living tissues). Therefore, a field of chemistry arose that studies these processes - physiological chemistry. Today it has turned into an independent science - biological chemistry, the data of which reveal the molecular mechanisms of physiological processes. In his experiments, a physiologist widely uses chemical methods, as well as methods that arose at the intersection of chemistry, physics and biology. These methods have given rise to new branches of science, for example biophysics, which studies the physical side of physiological phenomena.

The physiologist widely uses the method of labeled atoms. Modern physiological research also uses other methods borrowed from the exact sciences. They provide truly invaluable information when analyzing certain mechanisms of physiological processes.

Electrical recording of non-electrical quantities. Significant progress in physiology today is associated with the use of radio-electronic technology. Sensors are used - converters of various non-electrical phenomena and quantities (motion, pressure, temperature, concentration of various substances, ions, etc.) into electrical potentials, which are then amplified by electronic amplifiers and recorded by oscilloscopes. A huge number of different types of such recording devices have been developed, which make it possible to record many physiological processes on an oscilloscope. A number of devices use additional effects on the body (ultrasonic or electromagnetic waves, high-frequency electrical vibrations, etc.). In such cases, the change in the magnitude of the parameters of these effects that change certain physiological functions is recorded. The advantage of such devices is that the transducer-sensor can be mounted not on the organ being studied, but on the surface of the body. Waves, vibrations, etc. affecting the body. penetrate the body and, after affecting the function or organ under study, are recorded by a sensor. This principle is used, for example, to build ultrasonic flow meters that determine the speed of blood flow in vessels, rheographs and rheoplethysmographs that record changes in the amount of blood supply to various parts of the body, and many other devices. Their advantage is the ability to study the body at any time without preliminary operations. In addition, such studies do not harm the body. Most modern methods of physiological research in the clinic are based on these principles. In the USSR, the initiator of the use of radio-electronic technology for physiological research was Academician V.V. Parin.

A significant advantage of such recording methods is that the physiological process is converted by the sensor into electrical vibrations, and the latter can be amplified and transmitted via wire or radio to any distance from the object being studied. This is how telemetry methods arose, with the help of which it is possible in a ground laboratory to record physiological processes in the body of an astronaut in orbit, a pilot in flight, an athlete on the track, a worker during work, etc. The registration itself does not in any way interfere with the activities of the subjects.

However, the deeper the analysis of processes, the greater the need for synthesis arises, i.e. creating a whole picture of phenomena from individual elements.

The task of physiology is to, along with deepening the analysis, continuously carry out synthesis, to give a holistic picture of the body as a system.

The laws of physiology make it possible to understand the reaction of the body (as an integral system) and all its subsystems under certain conditions, under certain influences, etc.

Therefore, any method of influencing the body, before entering clinical practice, undergoes comprehensive testing in physiological experiments.

Acute experimental method. The progress of science is associated not only with the development of experimental technology and research methods. It greatly depends on the evolution of the thinking of physiologists, on the development of methodological and methodological approaches to the study of physiological phenomena. From the beginning until the 80s of the last century, physiology remained an analytical science. She divided the body into separate organs and systems and studied their activity in isolation. The main methodological technique of analytical physiology was experiments on isolated organs, or so-called acute experiments. Moreover, in order to gain access to any internal organ or system, the physiologist had to engage in vivisection (live section).

The animal was tied to a machine and a complex and painful operation was performed.

It was hard work, but science did not know any other way to penetrate deep into the body.

It was not only the moral side of the problem. Cruel torture and unbearable suffering to which the body was subjected grossly disrupted the normal course of physiological phenomena and did not make it possible to understand the essence of the processes that normally occur in natural conditions. The use of anesthesia and other methods of pain relief did not help significantly. Fixation of the animal, exposure to narcotic substances, surgery, blood loss - all this completely changed and disrupted the normal course of life. A vicious circle has formed. In order to study a particular process or function of an internal organ or system, it was necessary to penetrate into the depths of the organism, and the very attempt of such penetration disrupted the flow of vital processes, for the study of which the experiment was undertaken. In addition, the study of isolated organs did not provide an idea of ​​their true function in the conditions of a complete, undamaged organism.

Chronic experiment method. The greatest merit of Russian science in the history of physiology was that one of its most talented and bright representatives I.P.

Pavlov managed to find a way out of this impasse. I. P. Pavlov was very painful about the shortcomings of analytical physiology and acute experimentation. He found a way to look deep into the body without violating its integrity. This was a method of chronic experimentation carried out on the basis of “physiological surgery.”

On an anesthetized animal, under sterile conditions and in compliance with the rules of surgical technique, a complex operation was previously carried out, allowing access to one or another internal organ, a “window” was made into the hollow organ, a fistula tube was implanted, or the gland duct was brought out and sutured to the skin. The experiment itself began many days later, when the wound healed, the animal recovered and, in terms of the nature of the physiological processes, was practically no different from a normal healthy one. Thanks to the applied fistula, it was possible to study for a long time the course of certain physiological processes under natural behavioral conditions.

PHYSIOLOGY OF THE WHOLE ORGANISM

It is well known that science develops depending on the success of methods.

Pavlov's method of chronic experiment created a fundamentally new science - physiology of the whole organism, synthetic physiology, which was able to identify the influence of the external environment on physiological processes, detect changes in the functions of various organs and systems to ensure the life of the organism in various conditions.

With the advent of modern technical means for studying vital processes, it has become possible to study the functions of many internal organs, not only in animals, but also in humans, without preliminary surgical operations. “Physiological surgery” as a methodological technique in a number of branches of physiology turned out to be supplanted by modern methods of bloodless experiment. But the point is not in this or that specific technical technique, but in the methodology of physiological thinking. I.P. Pavlov created a new methodology, and physiology developed as a synthetic science and a systematic approach became organically inherent in it.

A complete organism is inextricably linked with its external environment, and therefore, as I.M. Sechenov wrote, the scientific definition of an organism should also include the environment that influences it. The physiology of the whole organism studies not only the internal mechanisms of self-regulation of physiological processes, but also the mechanisms that ensure continuous interaction and inextricable unity of the organism with the environment.

Regulation of vital processes, as well as the interaction of the body with the environment, is carried out on the basis of principles common to regulation processes in machines and automated production. These principles and laws are studied by a special field of science - cybernetics.

Physiology and cybernetics Cybernetics (from the Greek kybernetike - the art of control) is the science of managing automated processes. Control processes, as is known, are carried out by signals carrying certain information. In the body, such signals are nerve impulses of an electrical nature, as well as various chemicals.

Cybernetics studies the processes of perception, encoding, processing, storage and reproduction of information. In the body, there are special devices and systems for these purposes (receptors, nerve fibers, nerve cells, etc.).

Technical cybernetic devices have made it possible to create models that reproduce some functions of the nervous system. However, the functioning of the brain as a whole is not yet amenable to such modeling, and further research is needed.

The union of cybernetics and physiology arose only three decades ago, but during this time the mathematical and technical arsenal of modern cybernetics has provided significant advances in the study and modeling of physiological processes.

Mathematics and computer technology in physiology. Simultaneous (synchronous) registration of physiological processes allows for their quantitative analysis and study of the interaction between various phenomena. This requires precise mathematical methods, the use of which also marked a new important stage in the development of physiology. Mathematization of research allows the use of electronic computers in physiology. This not only increases the speed of information processing, but also makes it possible to carry out such processing directly at the time of the experiment, which allows you to change its course and the tasks of the study itself in accordance with the results obtained.

Thus, the spiral in the development of physiology seemed to have ended. At the dawn of this science, research, analysis and evaluation of the results were carried out by the experimenter simultaneously in the process of observation, directly during the experiment itself. Graphic registration made it possible to separate these processes in time and process and analyze the results after the end of the experiment.

Radioelectronics and cybernetics have made it possible to once again combine the analysis and processing of results with the conduct of the experiment itself, but on a fundamentally different basis: the interaction of many different physiological processes is simultaneously studied and the results of such interaction are analyzed quantitatively. This made it possible to conduct a so-called controlled automatic experiment, in which a computer helps the researcher not only analyze the results, but also change the course of the experiment and the formulation of tasks, as well as the types of effects on the body, depending on the nature of the body’s reactions that arise directly during the experiment. Physics, mathematics, cybernetics and other exact sciences have re-equipped physiology and provided the doctor with a powerful arsenal of modern technical means for accurately assessing the functional state of the body and for influencing the body.

Mathematical modeling in physiology. Knowledge of physiological patterns and quantitative relationships between various physiological processes made it possible to create their mathematical models. With the help of such models, these processes are reproduced on electronic computers, exploring various reaction options, i.e. their possible future changes under certain influences on the body (medicines, physical factors or extreme environmental conditions). Already, the union of physiology and cybernetics has proven useful during heavy surgical operations and in other emergency conditions that require an accurate assessment of both the current state of the body’s most important physiological processes and the anticipation of possible changes. This approach can significantly increase the reliability of the “human factor” in difficult and critical parts of modern production.

Physiology of the 20th century. has made significant progress not only in the field of revealing the mechanisms of life processes and controlling these processes. She made a breakthrough into the most complex and mysterious area - into the area of ​​psychic phenomena.

The physiological basis of the psyche - the higher nervous activity of humans and animals - has become one of the important objects of physiological research.

OBJECTIVE STUDY OF HIGHER NERVOUS ACTIVITY

For thousands of years, it was generally accepted that human behavior is determined by the influence of a certain intangible entity (“soul”), which a physiologist cannot comprehend.

I.M. Sechenov was the first physiologist in the world who dared to imagine behavior based on the principle of reflex, i.e. based on the mechanisms of nervous activity known in physiology. In his famous book “Reflexes of the Brain,” he showed that no matter how complex the external manifestations of human mental activity may seem to us, sooner or later they come down to only one thing - muscle movement.

“Whether a child smiles at the sight of a new toy, whether Garibaldi laughs when he is persecuted for excessive love for his homeland, whether Newton invents world laws and writes them on paper, whether a girl trembles at the thought of a first date, the end result of the thought is always one thing - muscular movement,” wrote I.M. Sechenov.

Analyzing the formation of a child’s thinking, I.M. Sechenov showed step by step that this thinking is formed as a result of influences from the external environment, combined with each other in various combinations, causing the formation of different associations.

Our thinking (spiritual life) is naturally formed under the influence of environmental conditions, and the brain is an organ that accumulates and reflects these influences. No matter how complex the manifestations of our mental life may seem to us, our internal psychological makeup is a natural result of the conditions of upbringing and environmental influences. 999/1000 of a person’s mental content depends on the conditions of upbringing, environmental influences in the broad sense of the word, wrote I.M. Sechenov, and only 1/1000 it is determined by congenital factors. Thus, the principle of determinism, the basic principle of the materialistic worldview, was first extended to the most complex area of ​​life phenomena, to the processes of human spiritual life. I.M. Sechenov wrote that someday a physiologist will learn to analyze the external manifestations of brain activity as accurately as a physicist can analyze a musical chord. I.M. Sechenov’s book was a work of genius, affirming materialistic positions in the most difficult spheres of human spiritual life.

Sechenov's attempt to substantiate the mechanisms of brain activity was a purely theoretical attempt. The next step was necessary - experimental studies of the physiological mechanisms underlying mental activity and behavioral reactions. And this step was taken by I.P. Pavlov.

The fact that it was I.P. Pavlov, and not someone else, who became the heir to the ideas of I.M. Sechenov and was the first to penetrate the basic secrets of the work of the higher parts of the brain is not accidental. The logic of his experimental physiological studies led to this. Studying vital processes in the body under conditions of natural animal behavior, I.

P. Pavlov drew attention to the important role of mental factors influencing all physiological processes. The observation of I. P. Pavlov did not escape the fact that saliva, I. M. SECHENOV gastric juice and other digestive juices begin to be released from the animal not only at the time of eating, but long before eating, at the sight of food, the sound of the steps of the attendant, who usually feeds the animal. I.P. Pavlov drew attention to the fact that appetite, the passionate desire for food, is as powerful a juice-secreting agent as food itself. Appetite, desire, mood, experiences, feelings - all these were mental phenomena. They were not studied by physiologists before I.P. Pavlov. I.P. Pavlov saw that the physiologist has no right to ignore these phenomena, since they powerfully interfere with the course of physiological processes, changing their character. Therefore, the physiologist was obliged to study them. But how? Before I.P. Pavlov, these phenomena were considered by a science called zoopsychology.

Having turned to this science, I.P. Pavlov had to move away from the solid ground of physiological facts and enter the realm of fruitless and groundless fortune-telling regarding the apparent mental state of animals. To explain human behavior, the methods used in psychology are legitimate, since a person can always report his feelings, moods, experiences, etc. Animal psychologists blindly transferred data obtained from examining humans to animals, and also talked about “feelings,” “moods,” “experiences,” “desires,” etc. in the animal, without being able to check whether this is true or not. For the first time in Pavlov's laboratories, as many opinions arose about the mechanisms of the same facts as there were observers who saw these facts. Each of them interpreted them in his own way, and there was no way to verify the correctness of any of the interpretations. I.P. Pavlov realized that such interpretations were meaningless and therefore took a decisive, truly revolutionary step. Without trying to guess about certain internal mental states of the animal, he began to study the animal’s behavior objectively, comparing certain effects on the body with the body’s responses. This objective method made it possible to identify the laws underlying the behavioral reactions of the body.

The method of objective study of behavioral reactions created a new science - the physiology of higher nervous activity with its precise knowledge of the processes occurring in the nervous system under certain influences of the external environment. This science has given a lot to understanding the essence of the mechanisms of human mental activity.

The physiology of higher nervous activity created by I. P. Pavlov became the natural science basis of psychology. It became the natural science basis of Lenin’s theory of reflection and is of utmost importance in philosophy, medicine, pedagogy and in all those sciences that one way or another face the need to study the inner (spiritual) world of man.

The importance of the physiology of higher nervous activity for medicine. Teachings of I.P.

Pavlov's theory of higher nervous activity is of great practical importance. It is known that a patient is cured not only by medicine, a scalpel or a procedure, but also by the doctor’s word, trust in him, and a passionate desire to get well. All these facts were known to Hippocrates and Avicenna. However, for thousands of years they were perceived as proof of the existence of a powerful, “God-given soul” that subjugates the “perishable body.” The teachings of I.P. Pavlov tore off the veil of mystery from these facts.

It became clear that the seemingly magical effect of talismans, a sorcerer or the spells of a shaman is nothing more than an example of the influence of the higher parts of the brain on internal organs and the regulation of all life processes. The nature of this influence is determined by the influence of environmental conditions on the body, the most important of which for humans are social conditions - in particular, the exchange of thoughts in human society through words. For the first time in the history of science, I.P. Pavlov showed that the power of words lies in the fact that words and speech represent a special system of signals, inherent only to humans, which naturally changes behavior and mental status. Paul's teaching expelled idealism from the last, seemingly impregnable refuge - the idea of ​​a God-given “soul.” It placed a powerful weapon in the hands of the doctor, giving him the opportunity to use words correctly, showing the most important role of moral influence on the patient for the success of treatment.

CONCLUSION

I.P. Pavlov can rightfully be considered the founder of modern physiology of the whole organism. Other outstanding Soviet physiologists also made a major contribution to its development. A. A. Ukhtomsky created the doctrine of the dominant as the basic principle of the activity of the central nervous system (CNS). L. A. Orbeli founded EvoluL. L. ORBELATIONAL physiology. He authored fundamental works on the adaptive-trophic function of the sympathetic nervous system. K. M. Bykov revealed the presence of conditioned reflex regulation of the functions of internal organs, showing that autonomic functions are not autonomous, that they are subject to the influence of the higher parts of the central nervous system and can change under the influence of conditioned signals. For humans, the most important conditioned signal is the word. This signal is capable of changing the activity of internal organs, which is of utmost importance for medicine (psychotherapy, deontology, etc.).

P.K. Anokhin developed the doctrine of the functional system - a universal scheme for the regulation of physiological processes and behavioral reactions in the physiology of the neuromuscular and central nervous systems. L. S. Stern is the author of the doctrine of the blood-brain barrier and histohematic barriers - regulators of immediate internal major discoveries in the field of regulation of the cardiovascular system (Larin reflex). He is in radio electronics, cybernetics, mathematics. E. A. Asratyan created a doctrine about the mechanisms of compensation for impaired functions. He is the author of a number of fundamental (1903-1971) creation of an artificial heart (A. A. Bryukhonenko), cosmic physiology, labor physiology, sports physiology, research into physiological mechanisms of adaptation, regulation and internal mechanisms for the implementation of many physiological functions. These and many other studies are of paramount importance for medicine.

Knowledge of vital processes occurring in various organs and tissues, mechanisms of regulation of life phenomena, understanding of the essence of the physiological functions of the body and the processes that interact with the environment represent the fundamental theoretical basis on which the training of the future doctor is based.

GENERAL PHYSIOLOGY

INTRODUCTION

Each of the hundred trillion cells of the human body has an extremely complex structure, the ability to self-organize and multilateral interaction with other cells. The number of processes carried out by each cell and the amount of information processed in this process far exceeds what takes place today in any large industrial plant. Nevertheless, the cell is only one of the relatively elementary subsystems in the complex hierarchy of systems that form a living organism.

All these systems are highly ordered. The normal functional structure of any of them and the normal existence of each element of the system (including each cell) are possible thanks to the continuous exchange of information between the elements (and between cells).

The exchange of information occurs through direct (contact) interaction between cells, as a result of the transport of substances with tissue fluid, lymph and blood (humoral communication - from the Latin humor - liquid), as well as during the transfer of bioelectric potentials from cell to cell, which represents the fastest way of transmitting information in the body. Multicellular organisms have developed a special system that provides perception, transmission, storage, processing and reproduction of information encoded in electrical signals. This is the nervous system that has reached its highest development in humans. To understand the nature of bioelectric phenomena, i.e., the signals by which the nervous system transmits information, it is necessary first of all to consider some aspects of the general physiology of the so-called excitable tissues, which include nervous, muscle and glandular tissue.

PHYSIOLOGY OF EXCITABLE TISSUE

All living cells have irritability, i.e. the ability, under the influence of certain factors of the external or internal environment, so-called stimuli, to move from a state of physiological rest to a state of activity. However, the term “excitable cells” is used only in relation to nerve, muscle and secretory cells that are capable of generating specialized forms of electrical potential oscillations in response to the action of a stimulus.

The first data on the existence of bioelectric phenomena (“animal electricity”) were obtained in the third quarter of the 18th century. at. studying the nature of the electrical discharge caused by some fish during defense and attack. A long-term scientific dispute (1791 -1797) between the physiologist L. Galvani and the physicist A. Volta about the nature of “animal electricity” ended with two major discoveries: facts were established indicating the presence of electrical potentials in nervous and muscle tissues, and a new method for obtaining electrical energy was discovered. current using dissimilar metals - a galvanic element (“voltaic column”) is created. However, the first direct measurements of potentials in living tissues became possible only after the invention of galvanometers. A systematic study of potentials in muscles and nerves in a state of rest and excitement was begun by Dubois-Reymond (1848). Further advances in the study of bioelectrical phenomena were closely related to the improvement of techniques for recording fast oscillations of electrical potential (string, loop and cathode oscilloscopes) and methods for their removal from single excitable cells. A qualitatively new stage in the study of electrical phenomena in living tissues - the 40-50s of our century. Using intracellular microelectrodes, it was possible to directly record the electrical potentials of cell membranes. Advances in electronics have made it possible to develop methods for studying ionic currents flowing through a membrane when the membrane potential changes or when biologically active compounds act on membrane receptors. In recent years, a method has been developed that makes it possible to record ion currents flowing through single ion channels.

The following main types of electrical responses of excitable cells are distinguished:

local response; spreading action potential and accompanying trace potentials; excitatory and inhibitory postsynaptic potentials; generator potentials, etc. All these potential fluctuations are based on reversible changes in the permeability of the cell membrane for certain ions. In turn, the change in permeability is a consequence of the opening and closing of ion channels existing in the cell membrane under the influence of an active stimulus.

The energy used in the generation of electrical potentials is stored in a resting cell in the form of concentration gradients of Na+, Ca2+, K+, Cl~ ions on both sides of the surface membrane. These gradients are created and maintained by the work of specialized molecular devices, so-called membrane ion pumps. The latter use for their work metabolic energy released during the enzymatic breakdown of the universal cellular energy donor - adenosine triphosphoric acid (ATP).

The study of electrical potentials accompanying the processes of excitation and inhibition in living tissues is important both for understanding the nature of these processes and for identifying the nature of disturbances in the activity of excitable cells in various types of pathology.

In modern clinics, methods for recording the electrical potentials of the heart (electrocardiography), brain (electroencephalography) and muscles (electromyography) have become especially widespread.

RESTING POTENTIAL

The term “membrane potential” (resting potential) is commonly used to refer to the transmembrane potential difference; existing between the cytoplasm and the external solution surrounding the cell. When a cell (fiber) is in a state of physiological rest, its internal potential is negative in relation to the external one, which is conventionally taken as zero. In different cells, the membrane potential varies from -50 to -90 mV.

To measure the resting potential and monitor its changes caused by one or another effect on the cell, the technique of intracellular microelectrodes is used (Fig. 1).

The microelectrode is a micropipette, that is, a thin capillary drawn from a glass tube. The diameter of its tip is about 0.5 microns. The micropipet is filled with saline solution (usually 3 M K.S1), a metal electrode (chlorinated silver wire) is immersed in it and connected to an electrical measuring device - an oscilloscope equipped with a direct current amplifier.

The microelectrode is installed over the object under study, for example, skeletal muscle, and then, using a micromanipulator - a device equipped with micrometer screws, is inserted into the cell. An electrode of normal size is immersed in a normal saline solution containing the tissue being examined.

As soon as the microelectrode pierces the surface membrane of the cell, the oscilloscope beam immediately deviates from its original (zero) position, thereby revealing the existence of a potential difference between the surface and the contents of the cell. Further advancement of the microelectrode inside the protoplasm does not affect the position of the oscilloscope beam. This indicates that the potential is indeed localized on the cell membrane.

If the microelectrode is successfully inserted, the membrane tightly covers its tip and the cell retains the ability to function for several hours without showing signs of damage.

There are many factors that change the resting potential of cells: the application of electric current, changes in the ionic composition of the medium, exposure to certain toxins, disruption of oxygen supply to tissue, etc. In all cases when the internal potential decreases (becomes less negative), we speak of membrane depolarization ; the opposite shift in potential (increasing the negative charge on the inner surface of the cell membrane) is called hyperpolarization.

NATURE OF RESTING POTENTIAL

Back in 1896, V. Yu. Chagovets put forward a hypothesis about the ionic mechanism of electrical potentials in living cells and made an attempt to apply Arrhenius’ theory of electrolytic dissociation to explain them. In 1902, Yu. Bernstein developed the membrane-ion theory, which was modified and experimentally substantiated by Hodgkin, Huxley and Katz (1949-1952). Currently, the latter theory enjoys universal acceptance. According to this theory, the presence of electrical potentials in living cells is due to the inequality in the concentration of Na+, K+, Ca2+ and C1~ ions inside and outside the cell and the different permeability of the surface membrane to them.

From the data in table. Figure 1 shows that the contents of the nerve fiber are rich in K+ and organic anions (which practically do not penetrate the membrane) and poor in Na+ and C1~.

The concentration of K+ in the cytoplasm of nerve and muscle cells is 40-50 times higher than in the external solution, and if the resting membrane were permeable only to these ions, then the resting potential would correspond to the equilibrium potassium potential (Ek), calculated using the Nernst formula :

where R is the gas constant, F is the Faraday number, T is the absolute temperature, Ko is the concentration of free potassium ions in the external solution, Ki is their concentration in the cytoplasm. To understand how this potential arises, consider the following model experiment (Fig. 2) .

Let's imagine a vessel separated by an artificial semi-permeable membrane. The pore walls of this membrane are electronegatively charged, so they allow only cations to pass through and are impermeable to anions. A saline solution containing K+ ions is poured into both halves of the vessel, but their concentration in the right part of the vessel is higher than in the left. As a result of this concentration gradient, K+ ions begin to diffuse from the right half of the vessel to the left, bringing their positive charge there. This leads to the fact that non-penetrating anions begin to accumulate near the membrane in the right half of the vessel. With their negative charge, they will electrostatically retain K+ at the surface of the membrane in the left half of the vessel. As a result, the membrane is polarized, and a potential difference is created between its two surfaces, corresponding to the equilibrium potassium potential. The assumption that at rest the membrane of nerve and muscle fibers is selectively permeable to K + and that it is their diffusion that creates the resting potential was made by Bernstein back in 1902 and confirmed by Hodgkin et al. in 1962 in experiments on isolated giant squid axons. The cytoplasm (axoplasm) was carefully squeezed out of a fiber with a diameter of about 1 mm, and the collapsed membrane was filled with an artificial saline solution. When the concentration of K+ in the solution was close to the intracellular one, a potential difference was established between the inner and outer sides of the membrane, close to the value of the normal resting potential (-50-=--- 80 mV), and the fiber conducted impulses. As the intracellular K+ concentration decreased and the external K+ concentration increased, the membrane potential decreased or even changed its sign (the potential became positive if the K+ concentration in the external solution was higher than in the internal one).

Such experiments have shown that the concentrated K+ gradient is indeed the main factor determining the magnitude of the resting potential of the nerve fiber. However, the resting membrane is permeable not only to K+, but (albeit to a much lesser extent) also to Na+. The diffusion of these positively charged ions into the cell reduces the absolute value of the internal negative potential of the cell created by K+ diffusion. Therefore, the resting potential of the fibers (-50 - 70 mV) is less negative than the potassium equilibrium potential calculated using the Nernst formula.

C1~ ions in nerve fibers do not play a significant role in the genesis of the resting potential, since the permeability of the resting membrane to them is relatively small. In contrast, in skeletal muscle fibers the permeability of the resting membrane for chlorine ions is comparable to potassium, and therefore the diffusion of C1~ into the cell increases the value of the resting potential. Calculated chlorine equilibrium potential (Ecl) at the ratio Thus, the value of the cell's resting potential is determined by two main factors: a) the ratio of the concentrations of cations and anions penetrating through the resting surface membrane; b) the ratio of membrane permeabilities for these ions.

To quantitatively describe this pattern, the Goldman-Hodgkin-Katz equation is usually used:

where Em is the resting potential, Pk, PNa, Pcl are the membrane permeability for K+, Na+ and C1~ ions, respectively; K0+ Na0+; Cl0- are the external concentrations of K+, Na+ and Cl- ions and Ki+ Nai+ and Cli- are their internal concentrations.

It was calculated that in an isolated squid giant axon at Em = -50 mV there is the following relationship between the ionic permeabilities of the resting membrane:

The equation explains many of the changes in the cell's resting potential observed experimentally and in natural conditions, for example, its persistent depolarization under the influence of certain toxins that cause an increase in sodium permeability of the membrane. These toxins include plant poisons: veratridine, aconitine, and one of the most powerful neurotoxins, batrachotoxin, produced by the skin glands of Colombian frogs.

Membrane depolarization, as follows from the equation, can also occur with unchanged PNA if the external concentration of K+ ions is increased (i.e., the Ko/Ki ratio is increased). This change in resting potential is by no means just a laboratory phenomenon. The fact is that the concentration of K+ in the intercellular fluid increases noticeably during the activation of nerve and muscle cells, accompanied by an increase in Pk. The concentration of K+ in the intercellular fluid increases especially significantly during disturbances of the blood supply (ischemia) to tissues, for example, myocardial ischemia. The resulting depolarization of the membrane leads to the cessation of the generation of action potentials, i.e., disruption of the normal electrical activity of cells.

ROLE OF METABOLISM IN GENESIS

AND MAINTAINING RESTING POTENTIAL

(SODIUM MEMBRANE PUMP)

Despite the fact that the fluxes of Na+ and K+ through the membrane at rest are small, the difference in the concentrations of these ions inside and outside the cell should eventually level out if there were no special molecular device in the cell membrane - the “sodium pump”, which provides removal (“pumping out”) of Na+ penetrating into the cytoplasm and introduction (“pumping”) K+ into the cytoplasm. The sodium pump moves Na+ and K+ against their concentration gradients, i.e. it does a certain amount of work. The direct source of energy for this work is an energy-rich (macroergic) compound - adenosine triphosphoric acid (ATP), which is a universal source of energy for living cells. The breakdown of ATP is carried out by protein macromolecules - the enzyme adenosine triphosphatase (ATPase), localized in the surface membrane of the cell. The energy released during the breakdown of one ATP molecule ensures the removal of three Na + ions from the cell in exchange for two K + ions entering the cell from the outside.

Inhibition of ATPase activity caused by certain chemical compounds (for example, the cardiac glycoside ouabain) disrupts the pump, causing the cell to lose K+ and become enriched in Na+. The same result is achieved by inhibition of oxidative and glycolytic processes in the cell, which ensure the synthesis of ATP. In experiments, this is achieved with the help of poisons that inhibit these processes. In conditions of impaired blood supply to tissues, weakening of the process of tissue respiration, the operation of the electrogenic pump is inhibited and, as a consequence, the accumulation of K+ in the intercellular gaps and depolarization of the membrane.

The role of ATP in the mechanism of active Na+ transport was directly proven in experiments on giant squid nerve fibers. It was found that by introducing ATP into the fiber, it was possible to temporarily restore the functioning of the sodium pump, impaired by the respiratory enzyme inhibitor cyanide.

Initially, it was believed that the sodium pump was electrically neutral, i.e., the number of exchanged Na+ and K+ ions was equal. It was later discovered that for every three Na+ ions removed from the cell, only two K+ ions enter the cell. This means that the pump is electrogenic: it creates a potential difference on the membrane that adds up to the resting potential.

This contribution of the sodium pump to the normal value of the resting potential is not the same in different cells: it is apparently insignificant in squid nerve fibers, but is significant for the resting potential (about 25% of the total value) in giant mollusk neurons and smooth muscles.

Thus, in the formation of the resting potential, the sodium pump plays a dual role: 1) creates and maintains a transmembrane concentration gradient of Na+ and K+; 2) generates a potential difference that is summed with the potential created by the diffusion of K+ along the concentration gradient.

ACTION POTENTIAL

An action potential is a rapid fluctuation in membrane potential that occurs when nerve, muscle, and some other cells are excited. It is based on changes in the ionic permeability of the membrane. The amplitude and nature of temporary changes in the action potential depend little on the strength of the stimulus that causes it; it is only important that this strength is not less than a certain critical value, which is called the threshold of irritation. Having arisen at the site of irritation, the action potential spreads along the nerve or muscle fiber without changing its amplitude.

The presence of a threshold and the independence of the amplitude of the action potential from the strength of the stimulus that caused it are called the “all or nothing” law.

Under natural conditions, action potentials are generated in nerve fibers when receptors are stimulated or nerve cells are excited. The propagation of action potentials along nerve fibers ensures the transmission of information in the nervous system. Upon reaching nerve endings, action potentials cause the secretion of chemicals (transmitters) that transmit a signal to muscle or nerve cells. In muscle cells, action potentials initiate a chain of processes that cause contraction. Ions that penetrate the cytoplasm during the generation of action potentials have a regulatory effect on cell metabolism and, in particular, on the processes of synthesis of proteins that make up ion channels and ion pumps.

To record action potentials, extra- or intracellular electrodes are used. In extracellular abduction, the electrodes are applied to the outer surface of the fiber (cell). This makes it possible to discover that the surface of the excited area for a very short time (in a nerve fiber for a thousandth of a second) becomes negatively charged in relation to the neighboring resting area.

The use of intracellular microelectrodes allows quantitative characterization of membrane potential changes during the rising and falling phases of the action potential. It has been established that during the ascending phase (depolarization phase), not only does the resting potential disappear (as was originally assumed), but a potential difference of the opposite sign occurs: the internal contents of the cell become positively charged in relation to the external environment, in other words, a reversal of the membrane potential occurs . During the descending phase (repolarization phase), the membrane potential returns to its original value. In Fig. Figures 3 and 4 show examples of recordings of action potentials in frog skeletal muscle fiber and squid giant axon. It can be seen that at the moment of reaching the apex (peak), the membrane potential is + 30 / + 40 mV and the peak oscillation is accompanied by long-term trace changes in the membrane potential, after which the membrane potential is established at the initial level. The duration of the action potential peak in various nerve and skeletal muscle fibers varies. 5. Summation of trace potentials in the phrenic nerve of a cat during its short-term dependence on temperature: when cooled by 10 °C, the duration of the peak increases approximately 3 times.

The changes in membrane potential following the peak of the action potential are called trace potentials.

There are two types of trace potentials - trace depolarization and trace hyperpolarization. The amplitude of trace potentials usually does not exceed several millivolts (5-10% of the peak height), and their duration in different fibers ranges from several milliseconds to tens and hundreds of seconds.

The dependence of the peak of the action potential and the trace depolarization can be considered using the example of the electrical response of skeletal muscle fiber. From the entry shown in Fig. 3, it can be seen that the descending phase of the action potential (repolarization phase) is divided into two unequal parts. Initially, the potential drop occurs quickly, and then slows down significantly. This slow component of the descending phase of the action potential is called trail depolarization.

An example of the trace membrane hyperpolarization accompanying the peak of an action potential in a single (isolated) squid giant nerve fiber is shown in Fig. 4. In this case, the descending phase of the action potential directly passes into the phase of trace hyperpolarization, the amplitude of which in this case reaches 15 mV. Trace hyperpolarization is characteristic of many non-pulp nerve fibers of cold-blooded and warm-blooded animals. In myelinated nerve fibers, trace potentials are more complex. A trace depolarization can turn into a trace hyperpolarization, then sometimes a new depolarization occurs, only after which the resting potential is completely restored. Trace potentials, to a much greater extent than peaks of action potentials, are sensitive to changes in the initial resting potential, ionic composition of the environment, oxygen supply to the fiber, etc.

A characteristic feature of trace potentials is their ability to change during the process of rhythmic impulses (Fig. 5).

IONIC MECHANISM OF ACTION POTENTIAL APPEARANCE

The action potential is based on changes in the ionic permeability of the cell membrane that develop sequentially over time.

As noted, at rest the permeability of the membrane to potassium exceeds its permeability to sodium. As a result, the flow of K+ from the cytoplasm into the external solution exceeds the oppositely directed flow of Na+. Therefore, the outer side of the membrane at rest has a positive potential relative to the inner one.

When a cell is exposed to an irritant, the permeability of the membrane to Na+ increases sharply and ultimately becomes approximately 20 times greater than the permeability to K+. Therefore, the flow of Na+ from the external solution into the cytoplasm begins to exceed the outward potassium current. This leads to a change in the sign (reversion) of the membrane potential: the internal contents of the cell become positively charged relative to its outer surface. This change in membrane potential corresponds to the ascending phase of the action potential (depolarization phase).

The increase in membrane permeability to Na+ lasts only for a very short time. Following this, the permeability of the membrane for Na+ decreases again, and for K+ it increases.

The process leading to the decline earlier Fig. 6. The time course of changes in sodium (g) increased sodium permeability and potassium (gk) permeability of the giant membrane is called sodium inactivation. squid axon during potential generation. As a result of inactivation, Na+ flows into the action cialis (V).

cytoplasm is sharply weakened. An increase in potassium permeability causes an increase in the flow of K+ from the cytoplasm into the external solution. As a result of these two processes, membrane repolarization occurs: the internal contents of the cell again acquire a negative charge in relation to the external solution. This change in potential corresponds to the descending phase of the action potential (repolarization phase).

One of the important arguments in favor of the sodium theory of the origin of action potentials was the fact that its amplitude was closely dependent on the Na+ concentration in the external solution.

Experiments on giant nerve fibers perfused from the inside with saline solutions provided direct confirmation of the correctness of the sodium theory. It has been established that when the axoplasm is replaced with a saline solution rich in K+, the fiber membrane not only maintains the normal resting potential, but for a long time retains the ability to generate hundreds of thousands of action potentials of normal amplitude. If K+ in the intracellular solution is partially replaced by Na+ and thereby reduces the Na+ concentration gradient between the external environment and the internal solution, the amplitude of the action potential sharply decreases. When K+ is completely replaced by Na+, the fiber loses its ability to generate action potentials.

These experiments leave no doubt that the surface membrane is indeed the site of potential occurrence both at rest and during excitation. It becomes obvious that the difference in concentrations of Na+ and K+ inside and outside the fiber is the source of the electromotive force that causes the occurrence of the resting potential and the action potential.

In Fig. Figure 6 shows changes in membrane sodium and potassium permeability during action potential generation in the squid giant axon. Similar relationships occur in other nerve fibers, nerve cell bodies, as well as in the skeletal muscle fibers of vertebrates. In the skeletal muscles of crustaceans and the smooth muscles of vertebrates, Ca2+ ions play a leading role in the genesis of the ascending phase of the action potential. In myocardial cells, the initial rise in the action potential is associated with an increase in membrane permeability for Na+, and the plateau of the action potential is due to an increase in membrane permeability for Ca2+ ions.

ABOUT THE NATURE OF IONIC PERMEABILITY OF THE MEMBRANE. ION CHANNELS

The considered changes in the ionic permeability of the membrane during the generation of an action potential are based on the processes of opening and closing of specialized ion channels in the membrane, which have two important properties: 1) selectivity towards certain ions; 2) electrical excitability, i.e. the ability to open and close in response to changes in membrane potential. The process of opening and closing a channel is probabilistic in nature (the membrane potential only determines the probability of the channel being in an open or closed state).

Like ion pumps, ion channels are formed by protein macromolecules that penetrate the lipid bilayer of the membrane. The chemical structure of these macromolecules has not yet been deciphered, so ideas about the functional organization of channels are still constructed mainly indirectly - based on the analysis of data obtained from studies of electrical phenomena in membranes and the influence of various chemical agents (toxins, enzymes, drugs, etc.) on the channels .). It is generally accepted that the ion channel consists of the transport system itself and the so-called gating mechanism (“gate”), controlled by the electric field of the membrane. The “gate” can be in two positions: it is completely closed or completely open, so the conductivity of a single open channel is a constant value.

The total conductivity of the membrane for a particular ion is determined by the number of simultaneously open channels permeable to a given ion.

This position can be written as follows:

where gi is the total permeability of the membrane for intracellular ions; N is the total number of corresponding ion channels (in a given region of the membrane); a - is the proportion of open channels; y is the conductivity of a single channel.

According to their selectivity, electrically excitable ion channels of nerve and muscle cells are divided into sodium, potassium, calcium, and chloride. This selectivity is not absolute:

the name of the channel indicates only the ion for which the channel is most permeable.

Through open channels, ions move along concentration and electrical gradients. These ion flows lead to changes in membrane potential, which in turn changes the average number of open channels and, accordingly, the magnitude of ionic currents, etc. This circular connection is important for the generation of the action potential, but it makes it impossible to quantify the dependence of ionic conductances on the magnitude of the generated potential . To study this dependence, the “potential fixation method” is used. The essence of this method is to forcibly maintain the membrane potential at any given level. Thus, by applying a current to the membrane that is equal in magnitude, but opposite in sign to the ionic current passing through open channels, and measuring this current at different potentials, researchers are able to trace the dependence of the potential on the ionic conductivities of the membrane (Fig. 7). Time course of changes in sodium (gNa) and potassium (gK) membrane permeability upon depolarization of the axon membrane by 56 mV.

a - solid lines show permeability during long-term depolarization, and dotted lines - during membrane repolarization after 0.6 and 6.3 ms; b dependence of the peak value of sodium (gNa) and steady-state level of potassium (gK) permeability on the membrane potential.

Rice. 8. Schematic representation of an electrically excitable sodium channel.

Channel (1) is formed by a macromolecule of protein 2), the narrowed part of which corresponds to a “selective filter”. The channel has activation (m) and inactivation (h) “gates”, which are controlled by the electric field of the membrane. At the resting potential (a), the most probable position is “closed” for the activation gate and the “open” position for the inactivation gate. Depolarization of the membrane (b) leads to the rapid opening of the t-“gate” and the slow closing of the h-“gate”, therefore, at the initial moment of depolarization, both pairs of “gates” are open and ions can move through the channel accordingly There are substances with their concentrations of ionic and electrical gradients. With continued depolarization, the inactivation “gate” closes and the channel goes into the inactivation state.

branes. In order to isolate from the total ionic current flowing through the membrane its components corresponding to ion flows, for example, through sodium channels, chemical agents are used that specifically block all other channels. Proceed accordingly when measuring potassium or calcium currents.

In Fig. Figure 7 shows changes in sodium (gNa) and potassium (gK) permeability of the nerve fiber membrane during fixed depolarization. As noted, the gNa and gK values ​​reflect the number of simultaneously open sodium or potassium channels.

As can be seen, gNa quickly, in a fraction of a millisecond, reached a maximum, and then slowly began to decrease to the initial level. After the end of depolarization, the ability of sodium channels to reopen is gradually restored over tens of milliseconds.

To explain this behavior of sodium channels, it has been suggested that there are two types of “gates” in each channel.

Fast activation and slow inactivation. As the name suggests, the initial rise in gNa is associated with the opening of the activation gate (the “activation process”), and the subsequent fall in gNa, during ongoing membrane depolarization, is associated with the closing of the inactivation gate (the “inactivation process”).

In Fig. 8, 9 schematically depict the organization of the sodium channel, facilitating the understanding of its functions. The channel has external and internal expansions (“mouths”) and a short narrowed section, the so-called selective filter, in which cations are “selected” according to their size and properties. Judging by the size of the largest cation penetrating through the sodium channel, the filter opening is no less than 0.3-0.nm. When passing through the filter fig. 9. State of sodium and potassium ka-ions Na+ lose part of their hydration shell. nals in various phases of potentials of action-Activation (t) and inactivation (h) “thefts (diagram). Explanation in the text.

ta* are located in the region of the inner end of the sodium channel, with the “gate” h facing the cytoplasm. This conclusion was reached based on the fact that the application of certain proteolytic enzymes (pronase) to the inner side of the membrane eliminates sodium inactivation (destroys the h-gate).

At rest, the "gate" t is closed, while the "gate" h is open. During depolarization, at the initial moment the “gates” t and h are open - the channel is in a conducting state. Then the inactivation gate closes and the channel is inactivated. After the end of depolarization, the “gate” h slowly opens, and the “gate” t quickly closes and the channel returns to its original resting state.

A specific sodium channel blocker is tetrodotoxin, a compound synthesized in the tissues of some species of fish and salamanders. This compound enters the outer mouth of the channel, binds to some as yet unidentified chemical groups and “clogs” the channel. Using radioactively labeled tetrodotoxin, the density of sodium channels in the membrane was calculated. In different cells, this density varies from tens to tens of thousands of sodium channels per square micron of membrane.

The functional organization of potassium channels is similar to that of sodium channels, the only differences being their selectivity and the kinetics of activation and inactivation processes.

The selectivity of potassium channels is higher than the selectivity of sodium channels: for Na+, potassium channels are practically impermeable; the diameter of their selective filter is about 0.3 nm. Activation of potassium channels has approximately an order of magnitude slower kinetics than activation of sodium channels (see Fig. 7). During 10 ms of depolarization, gK does not show a tendency to inactivation: potassium inactivation develops only with multi-second depolarization of the membrane.

It should be emphasized that such relationships between the processes of activation and inactivation of potassium channels are characteristic only of nerve fibers. In the membrane of many nerve and muscle cells there are potassium channels that are relatively quickly inactivated. Rapidly activated potassium channels have also been discovered. Finally, there are potassium channels that are activated not by the membrane potential, but by intracellular Ca2+.

Potassium channels are blocked by the organic cation tetraethylammonium, as well as aminopyridines.

Calcium channels are characterized by slow kinetics of activation (milliseconds) and inactivation (tens and hundreds of milliseconds). Their selectivity is determined by the presence in the area of ​​the outer mouth of some chemical groups that have an increased affinity for divalent cations: Ca2+ binds to these groups and only after that passes into the channel cavity. For some divalent cations, the affinity for these groups is so great that when they bind to them, they block the movement of Ca2+ through the channel. This is how Mn2+ works. Calcium channels can also be blocked by certain organic compounds (verapamil, nifedipine) used in clinical practice to suppress increased electrical activity of smooth muscles.

A characteristic feature of calcium channels is their dependence on metabolism and, in particular, on cyclic nucleotides (cAMP and cGMP), which regulate the processes of phosphorylation and dephosphorylation of calcium channel proteins.

The rate of activation and inactivation of all ion channels increases with increasing membrane depolarization; Accordingly, the number of simultaneously open channels increases to a certain limit.

MECHANISMS OF CHANGES IN IONIC CONDUCTIVITY

DURING ACTION POTENTIAL GENERATION

It is known that the ascending phase of the action potential is associated with an increase in sodium permeability. The process of increasing g Na develops as follows.

In response to the initial membrane depolarization caused by the stimulus, only a small number of sodium channels open. Their opening, however, results in a flow of Na+ ions entering the cell (incoming sodium current), which increases the initial depolarization. This leads to the opening of new sodium channels, i.e., to a further increase in gNa, respectively, of the incoming sodium current, and consequently, to further depolarization of the membrane, which, in turn, causes an even greater increase in gNa, etc. Such a circular avalanche-like process called regenerative (i.e., self-renewing) depolarization.

Schematically it can be depicted as follows:

Theoretically, regenerative depolarization should end with an increase in the internal potential of the cell to the value of the equilibrium Nernst potential for Na+ ions:

where Na0+ is the external, and Nai+ is the internal concentration of Na+ ions. At the observed ratio, this value is the limiting value for the action potential. In reality, however, the peak potential never reaches the value ENa, firstly, because the membrane at the moment of the peak of the action potential is permeable not only to Na+ ions, but also to K+ ions (to a much lesser extent). Secondly, the rise of the action potential to the ENa value is counteracted by restoration processes leading to restoration of the original polarization (membrane repolarization).

Such processes are a decrease in the value of gNa and an increase in the level of g K. The decrease in gNa is due to the fact that the activation of sodium channels during depolarization is replaced by their inactivation; this leads to a rapid decrease in the number of open sodium channels. At the same time, under the influence of depolarization, slow activation of potassium channels begins, causing an increase in the gk value. A consequence of an increase in gK is an increase in the flow of K+ ions leaving the cell (outgoing potassium current).

Under conditions of decreased gNa associated with inactivation of sodium channels, the outgoing current of K+ ions leads to repolarization of the membrane or even to its temporary (“trace”) hyperpolarization, as occurs, for example, in the squid giant axon (see Fig. 4) .

Membrane repolarization in turn leads to the closure of potassium channels and, consequently, a weakening of the outward potassium current. At the same time, under the influence of repolarization, sodium inactivation is slowly eliminated:

the inactivation gate opens and the sodium channels return to the resting state.

In Fig. Figure 9 schematically shows the state of sodium and potassium channels during various phases of action potential development.

All agents that block sodium channels (tetrodotoxin, local anesthetics and many other drugs) reduce the slope and amplitude of the action potential, and to a greater extent, the higher the concentration of these substances.

ACTIVATION OF SODIUM-POTASSIUM PUMP

WHEN EXCITED

The occurrence of a series of impulses in a nerve or muscle fiber is accompanied by an enrichment of protoplasm in Na+ and loss of K+. For a giant squid axon with a diameter of 0.5 mm, it is calculated that during a single nerve impulse, about 20,000 Na+ enters the protoplasm through each square micron of membrane and the same amount of K+ leaves the fiber. As a result, with each impulse the axon loses about one millionth of its total potassium content. Although these losses are very insignificant, with the rhythmic repetition of pulses, when added up, they should lead to more or less noticeable changes in concentration gradients.

Such concentration shifts should develop especially quickly in thin nerve and muscle fibers and small nerve cells that have a small volume of cytoplasm relative to the surface. This, however, is counteracted by the sodium pump, whose activity increases with increasing intracellular concentration of Na+ ions.

Increased pump operation is accompanied by a significant increase in the intensity of metabolic processes that supply energy for the active transfer of Na+ and K+ ions across the membrane. This is manifested by increased processes of breakdown and synthesis of ATP and creatine phosphate, increased oxygen consumption by the cell, increased heat production, etc.

Thanks to the operation of the pump, the inequality of concentrations of Na+ and K+ on both sides of the membrane, which was disrupted during excitation, is completely restored. It should, however, be emphasized that the rate of removal of Na+ from the cytoplasm using a pump is relatively low: it is approximately 200 times lower than the rate of movement of these ions through the membrane along the concentration gradient.

Thus, in a living cell there are two systems for the movement of ions through the membrane (Fig. 10). One of them is carried out along an ion concentration gradient and does not require energy, so it is called passive ion transport. It is responsible for the occurrence of the resting potential and the action potential and ultimately leads to equalization of the concentration of ions on both sides of the cell membrane. The second type of ion movement through the membrane, which occurs against a concentration gradient, consists of “pumping” sodium ions from the cytoplasm and “pumping” potassium ions into the cell. This type of ion transport is possible only if metabolic energy is consumed. It is called active ion transport. It is responsible for maintaining a constant difference in ion concentrations between the cytoplasm and the fluid surrounding the cell. Active transport is the result of the work of the sodium pump, thanks to which the initial difference in ion concentrations, which is disrupted with each outbreak of excitation, is restored.

MECHANISM OF CELL (FIBER) IRRITATION

ELECTRIC SHOCK

Under natural conditions, the generation of an action potential is caused by so-called local currents that arise between the excited (depolarized) and resting sections of the cell membrane. Therefore, electric current is considered as an adequate stimulus for excitable membranes and is successfully used in experiments to study the patterns of occurrence of action potentials.

The minimum current strength necessary and sufficient to initiate an action potential is called threshold; accordingly, stimuli of greater and lesser strength are designated subthreshold and suprathreshold. The threshold current strength (threshold current), within certain limits, is inversely related to the duration of its action. There is also a certain minimum slope of the current increase, below which the latter loses the ability to cause an action potential.

There are two ways to apply current to tissues to measure the threshold of stimulation and, therefore, to determine their excitability. In the first method - extracellular - both electrodes are placed on the surface of the irritated tissue. It is conventionally assumed that the applied current enters the tissue in the anode region and exits in the cathode region (Fig. 1 1). The disadvantage of this method of measuring the threshold is the significant branching of the current: only part of it passes through the cell membranes, while part branches off into the intercellular gaps. As a result, during irritation it is necessary to apply a current of much greater strength than is necessary to cause excitation.

In the second method of supplying current to cells - intracellular - a microelectrode is inserted into the cell, and a regular electrode is applied to the surface of the tissue (Fig. 12). In this case, all the current passes through the cell membrane, which allows you to accurately determine the smallest current required to cause an action potential. With this method of stimulation, potentials are removed using a second intracellular microelectrode.

The threshold current required to cause excitation of various cells with an intracellular stimulating electrode is 10 - 7 - 10 - 9 A.

In laboratory conditions and in some clinical studies, electrical stimuli of various shapes are used to irritate nerves and muscles: rectangular, sinusoidal, linearly and exponentially increasing, inductive shocks, capacitor discharges, etc.

The mechanism of the irritating effect of current for all types of stimuli is in principle the same, but in its most distinct form it is revealed when using direct current.

EFFECT OF DC CURRENT ON EXCITABLE TISSUE

Polar law of irritation When a nerve or muscle is irritated by direct current, excitation occurs at the moment the direct current closes only under the cathode, and at the moment it opens, only under the anode. These facts are united under the name of the polar law of irritation, discovered by Pflueger in 1859. The polar law is proven by the following experiments. The area of ​​the nerve under one of the electrodes is killed, and the second electrode is installed on the undamaged area. If the cathode comes into contact with the undamaged area, excitation occurs at the moment the current closes; if the cathode is installed on a damaged area, and the anode on an undamaged area, excitation occurs only when the current is interrupted. The irritation threshold during opening, when excitation occurs under the anode, is significantly higher than during closing, when excitation occurs under the cathode.

The study of the mechanism of the polar action of electric current became possible only after the described method of simultaneous introduction of two microelectrodes into cells was developed: one for stimulation, the other for removing potentials. It was found that an action potential occurs only if the cathode is outside and the anode is inside the cell. With the reverse arrangement of the poles, i.e., the outer anode and the inner cathode, excitation does not occur when the current is closed, no matter how strong it is. Corporate presentation Corporate presentation “Integrated energy systems”: a new approach to energy July 2005 Corporate presentation About IES- Holding Private company CJSC IES (Integrated Energy Systems) was created in December 2002 to implement strategic investment programs in the Russian electric power industry. Over the two years of its existence, CJSC IES has invested about 300 million US dollars in the energy industry. CJSC IES represents the interests of shareholders who own...”

“Ministry of Education of the Republic of Belarus Educational and methodological association of universities of the Republic of Belarus for natural science education APPROVED by the First Deputy Minister of Education of the Republic of Belarus A.I. Zhuk _ 2009 Registration No. TD -/type. PHYSICAL CHEMISTRY Typical curriculum for higher educational institutions in the specialty: 1-31 05 01 Chemistry (in areas) Areas of specialty: 1-31 05 01-01 scientific and production activities 1-31 05 01-02 scientific and pedagogical..."

“CO 6.018 Records are made and used in CO 1.004 Provided in CO 1.023. Federal State Budgetary Educational Institution of Higher Professional Education Saratov State Agrarian University named after N.I. Vavilova Faculty of Veterinary Medicine and Biotechnology AGREED BY APPROVED Dean of the Faculty of FVM and BT Vice-Rector for Academic Affairs Molchanov A.V. Larionov S.V. _ year _ year WORKING (MODULAR) PROGRAM in the discipline Organization and economics of veterinary...”

“CONTENTS 1 GENERAL PROVISIONS 1.1 The main professional educational program of higher education (OPOP HE) of the bachelor's degree, implemented by the university in the field of training 080100.62 Economics and the training profile Banking. 1.2 Regulatory documents for the development of bachelor's OPOP in the field of study 080100.62 Economics and training profile Banking. 1.3 General characteristics of the university OPOP HE bachelor’s degree 1.4 Requirements for applicants 2 PROFESSIONAL CHARACTERISTICS...”

“Ministry of Education and Science of the Russian Federation State Educational Institution of Higher Professional Education Altai State University APPROVED by Dean of the Faculty of History _ _ 2011 WORK PROGRAM for the discipline World integration processes and international organizations for the specialty International Relations Faculty of History Department of General History and International Relations course IV semester 7 lectures 50 hours Exam in the 7th semester Practical (seminar) classes 22 hours Total hours 72 hours Independent work 72 hours Total.. ."

"MOSCOW STATE UNIVERSITY NAMED AFTER M.V. LOMONOSOV FACULTY OF GEOLOGY Direction GEOLOGY Master's program CRYSTALLOGRAPHY Department of CRYSTALLOGRAPHY AND CRYSTALLOCHEMISTRY BACHELOR'S THESIS Computer modeling of the radiation resistance of solid solutions of oxides with a perovskite structure by the method molecular dynamics Computer modeling of perovskite type oxides solid solutions radiation resistance by the molecular dynamics method Protasov Nikolay Mikhailovich Academician of the Russian Academy of Sciences,...”

“Federal State Budgetary Educational Institution of Higher Professional Education St. Petersburg National Research University of Information Technologies, Mechanics and Optics I APPROVED Responsible for the direction of training: Parfenov V.G., Doctor of Technical Sciences, Prof., Dean of FITiP LIST OF EXAMINATION QUESTIONS for the master’s degree program Supercomputer Technologies in Interdisciplinary Research Department of High Performance Computing Differential Equations 1...."

“Educational institution International State Ecological University named after A.D. Sakharov APPROVED by the Vice-Rector for Academic Affairs of Moscow State Economic University named after. HELL. Sakharova O.I. Rodkin 2013 Registration No. UD -_/r. ECOLOGY OF THE URBAN ENVIRONMENT Curriculum of a higher education institution in the academic discipline for specialty 1-33 01 01 Bioecology Faculty of Environmental Medicine Department of Human Biology and Ecology Course Semester Lectures 24 hours Exam semester Laboratory classes 12 hours Classroom..."

“Ministry of Education and Science of the Russian Federation Federal State Budgetary Educational Institution of Higher Professional Education Tomsk State University of Control Systems and Radioelectronics. (TUSUR) APPROVED by Vice-Rector for Academic Affairs _ L.A. Bokov __ 2011 WORK PROGRAM In the discipline Programming (name of discipline) For training specialists in specialty 220601.65 Innovation Management and bachelors in specialty 220600.62...”

« employees and graduate students CURRENT PROBLEMS OF ECOLOGY AND EVOLUTION IN RESEARCH OF YOUNG SCIENTISTS PROGRAM PRELIMINARY PROGRAM FOR DISTRIBUTION WITH THE SECOND INFORMATION LETTER COLLECTION OF APPLICATIONS FOR PARTICIPATION UNTIL FEBRUARY 24 April 23-25, 2014 9-30 to 19-00 hours IPEE RAS, Moscow Hall of the Branch of Biological Sciences of the Russian Academy of Sciences at the address: Moscow, Leninsky Prospekt, ..."

“preparation of sports reserves for national teams of the country; training masters of sports of international class, masters of sports of Russia, candidates for master of sports of Russia, athletes of the first category; to be a methodological center for the preparation of Olympic reserves based on the widespread development of this sport; provide assistance to children's and youth sports schools in the development of the species..."

“GENERAL CHEMISTRY PROGRAM FOR THE PROFILE CLASS OF GBOU Central Educational Institution No. 57 School No. 57 Explanatory Note This program is intended for the specialized group in chemistry of GBOU No. 57 School No. 57 and defines the content of the training course, implemented in full compliance with the federal component of the state educational standard. The program is based on the educational and methodological set of N.E. Kuznetsova, T.I. Litvinova and A.N. Levkina; completely satisfied..."

“MINISTRY OF HEALTH OF THE RUSSIAN FEDERATION State budgetary educational institution of higher professional education Orenburg State Medical Academy of the Ministry of Health of the Russian Federation APPROVED Vice-Rector for Scientific and Clinical Work Professor N.P. Setko _20 WORK PROGRAM of research work of the main professional educational program of postgraduate professional education (postgraduate studies) in scientific...”

“MINISTRY OF EDUCATION AND SCIENCE OF THE RUSSIAN FEDERATION Federal State Budgetary Educational Institution of Higher Professional Education KRASNOYARSK STATE PEDAGOGICAL UNIVERSITY named after. V.P. ASTAFIEV (Kazan State Pedagogical University named after V.P. Astafiev) Institute of Psychological and Pedagogical Education Entrance test program for applicants to graduate school Direction of preparation 06/37/01 Psychological sciences Postgraduate program Pedagogical psychology Krasnoyarsk - 2014...”

“The Vienna Ball in Moscow, held annually since 2003, is the largest and most famous ball in Russia and one of the largest balls in the world. Stars of world classical art and the best symphony and jazz orchestras take part in the Vienna Balls in Moscow. Guests of the Ball are politicians and diplomats, prominent cultural and scientific figures, representatives of the business community of Russia, Austria and other countries, have the opportunity not only to enjoy music and dancing, but also to establish new..."

“2 The curriculum is based on the standard curriculum for Orthopedic Dentistry, approved on September 14, 2010, registration No. TD-l.202 /type. Recommended for approval as a curriculum (working) at a meeting of the Department of Orthopedic Dentistry on August 31, 2010 (Minutes No. 1) Head of the Department, Professor S.A. Naumovich Approved as a curriculum (working) by the methodological commission of dental disciplines of the Belarusian educational institution. .."

“Appendix 3 to the PUP for the 2013-2014 academic year. Implemented educational programs for the 2013-2014 academic year. Class Number of Subjects Textbooks Training programs PUP 1. Training Primer R.N. Buneev UMK School-2100 1a.b 72 Lileva L.V. diploma Moscow Balass, 2012 Moscow Balass 2009 Malysheva O.A. auto R.N.Buneev UMK School-2. Russian language Buneev R.N. Moscow Balass, 2012 Moscow Balass 2009 auto. R.N.Buneev A small door to a large educational complex School-3. Literary reading world Moscow Balass 2009...”

"MINISTRY OF EDUCATION AND SCIENCE OF THE RUSSIAN FEDERATION Yaroslavl State University named after. P.G. Demidova Faculty of Social and Political Sciences APPROVED by Vice-Rector for Educational Development _E.V. Sapir _2012 Work program of the discipline of postgraduate professional education (postgraduate studies) History and philosophy of science in the specialty of scientists 09.00.11 Social philosophy Yaroslavl 2012 2 Goals of mastering the discipline History and philosophy science 1. The purpose of mastering the discipline History...”

“The Federal State Budgetary Educational Institution of Higher Professional Education Omsk State Technical University Work program in the Discipline of pricing (B. Z.V02.) Direction 080100.62 Economics Profile: Commerce was developed in accordance with the Ob in the direction of preparation of undergraduate studies 080100.62 E Konu prof ommercia. I The program was compiled by: Associate Professor of the Department of Economics and Labor Organization /// Lebedeva I.L. About the discussion at the meeting of the department...”

“PROGRAM Creating a comfortable urban environment in Perm 1 A city is a living organism and when everything is in order in it, it is healthy and functions effectively, and then it is comfortable for residents. This means that: - the city provides people with employment and a good stable income; - the city is developing (housing, roads are being built, business is developing, etc.); - the city provides a person with everything necessary (kindergartens, schools, hospitals, public transport, leisure, etc.); - the city has a low level...”

METHODS OF PHYSIOLOGICAL RESEARCH
Physiology is a science that studies the mechanisms of functioning of the body in its relationship with the environment (this is the science of the life activity of the organism), physiology is an experimental science and the main methods of physiological science are experimental methods. However, physiology as a science originated within medical science even before our era in Ancient Greece in the school of Hippocrates, when the main method of research was the observation method. Physiology emerged as an independent science in the 15th century thanks to the research of Harvey and a number of other natural scientists, and, starting from the late 15th and early 16th centuries, the main method in the field of physiology was the experimental method. I.N. Sechenov and I.P. Pavlov made a significant contribution to the development of methodology in the field of physiology, in particular in the development of a chronic experiment.

Literature:

1. 
   Human physiology. Kositsky
2. 
   Korbkov. Normal physiology.
3. 
   Zimkin. Human physiology.
4. 
   Human Physiology, ed. Pokrovsky V.N., 1998
5. 
   Physiology of GNI. Kogan.
6. 
   Physiology of humans and animals. Kogan. 2 t.
7. 
   Ed. Tkachenko P.I. Human physiology. 3 t.
8. 
   Ed. Nozdrocheva. Physiology. General course. 2 t.
9. 
   Ed. Kuraeva. 3 volumes. Translated textbook? human physiology.

Observation method- the most ancient, originated in Dr. Greece, was well developed in Egypt, on dr. East, in Tibet, in China. The essence of this method is long-term observation of changes in the functions and conditions of the body, recording these observations and, if possible, comparing visual observations with changes in the body after autopsy. In Egypt, during mummification, corpses were opened, the priest's observations of the patient: changes in the skin, depth and frequency of breathing, the nature and intensity of discharge from the nose, oral cavity, as well as the volume and color of urine, its transparency, the amount and nature of excreted feces, its color, pulse rate and other indicators, which were compared with changes in the internal organs, were recorded on papyrus. Thus, already by changing the feces, urine, sputum, etc. secreted by the body. it was possible to judge the dysfunction of a particular organ, for example, if the stool is white, it is possible to assume a dysfunction of the liver; if the stool is black or dark, then it is possible to assume gastric or intestinal bleeding. Additional criteria included changes in skin color and turgor, swelling of the skin, its character, color of the sclera, sweating, trembling, etc.

Hippocrates included the nature of behavior among the observable signs. Thanks to his careful observations, he formulated a doctrine of temperament, according to which all humanity is divided into 4 types according to behavioral characteristics: choleric, sanguine, phlegmatic, melancholic, but Hippocrates made a mistake in the physiological basis of the types. They based each type on the ratio of the main body fluids: sangvi - blood, phlegm - tissue fluid, cholea - bile, melancholea - black bile. The scientific theoretical basis for temperaments was given by Pavlov as a result of long-term experimental studies and it turned out that the basis of temperament is not the ratio of fluids, but the ratio of nervous processes of excitation and inhibition, the degree of their severity and the predominance of one process over another, as well as the rate of replacement of one process by others.

The observation method is widely used in physiology (especially in psychophysiology) and currently the observation method is combined with the method of chronic experiment.

Experimental method. A physiological experiment, in contrast to simple observation, is a targeted intervention in the current functioning of the body, designed to clarify the nature and properties of its functions, their relationships with other functions and with environmental factors. Also, the intervention often requires surgical preparation of the animal, which can have: 1) acute (vivisection, from the word vivo - living, sekcia - sec, i.e. slashing of the living), 2) chronic (experimental-surgical) forms.

In this regard, the experiment is divided into 2 types: acute (vivisection) and chronic. A physiological experiment allows you to answer the questions: what happens in the body and how it happens.

Vivisection is a form of experimentation performed on an immobilized animal. Vivisection was first used in the Middle Ages, but began to be widely introduced into physiological science during the Renaissance (XV-XVII centuries). Anesthesia was unknown at that time and the animal was rigidly fixed by 4 limbs, while it experienced torture and uttered heartbreaking screams. The experiments were carried out in special rooms, which people dubbed “devilish”. This was the reason for the emergence of philosophical groups and movements. Animalism (trends promoting humane treatment of animals and advocating for an end to cruelty to animals; animalism is currently being promoted), vitalism (advocated that experiments were not carried out on non-anesthetized animals and volunteers), mechanism (identified processes occurring correctly in animals with processes in inanimate nature, a prominent representative of mechanism was the French physicist, mechanic and physiologist Rene Descartes), anthropocentrism.

Beginning in the 19th century, anesthesia began to be used in acute experiments. This led to a disruption of regulatory processes on the part of the higher processes of the central nervous system, as a result of which the integrity of the body’s response and its connection with the external environment is disrupted. This use of anesthesia and surgical persecution during vivisection introduces uncontrolled parameters into an acute experiment that are difficult to take into account and predict. An acute experiment, like any experimental method, has its advantages: 1) vivisection is one of the analytical methods, makes it possible to simulate different situations, 2) vivisection makes it possible to obtain results in a relatively short time; and disadvantages: 1) in an acute experiment, consciousness is switched off when anesthesia is used and, accordingly, the integrity of the body’s response is disrupted, 2) the body’s connection with the environment is disrupted when anesthesia is used, 3) in the absence of anesthesia, there is a release of stress hormones and endogenous (produced) hormones that are inadequate to the normal physiological state. inside the body) morphine-like substances endorphins, which have an analgesic effect.

All this contributed to the development of a chronic experiment - long-term observation after acute intervention and restoration of relationships with the environment. Advantages of a chronic experiment: the body is as close as possible to the conditions of intensive existence. Some physiologists consider the disadvantages of a chronic experiment to be that the results are obtained over a relatively long period of time.

The chronic experiment was first developed by Russian physiologist I.P. Pavlov, and, since the end of the 18th century, has been widely used in physiological research. In a chronic experiment, a number of methodological techniques and approaches are used.

The method developed by Pavlov is a method of applying fistulas to hollow organs and organs that have excretory ducts. The founder of the fistula method was Basov, however, when applying a fistula using his method, the contents of the stomach entered the test tube along with digestive juices, which made it difficult to study the composition of gastric juice, the stages of digestion, the speed of the digestion process and the quality of the separated gastric juice for different food compositions.

Fistulas can be placed on the stomach, ducts of the salivary glands, intestines, esophagus, etc. The difference between Pavlov’s fistula and Basov’s is that Pavlov placed the fistula on a “small ventricle”, artificially made surgically and preserving digestive and humoral regulation. This allowed Pavlov to identify not only the qualitative and quantitative composition of gastric juice for food taken, but also the mechanisms of nervous and humoral regulation of digestion in the stomach. In addition, this allowed Pavlov to identify 3 stages of digestion:

1. 
   conditioned reflex - with it, appetizing or “incendiary” gastric juice is released;
2. 
   unconditioned reflex phase - gastric juice is released onto the incoming food, regardless of its qualitative composition, because in the stomach there are not only chemoreceptors, but also non-chemoreceptors that respond to the volume of food,
3. 
   intestinal phase - after food enters the intestines, digestion intensifies.

For his work in the field of digestion, Pavlov was awarded the Nobel Prize.
Heterogeneous neurovascular or neuromuscular anasthenoses. This is a change in the effector organ in the genetically determined nervous regulation of functions. Carrying out such anasthenoses makes it possible to identify the absence or presence of plasticity of neurons or nerve centers in the regulation of functions, i.e. can the sciatic nerve with the remainder of the spine control the respiratory muscles.

In neurovascular anasthenoses, the effector organs are blood vessels and the chemo- and baroreceptors located in them, respectively. Anasthenoses can be performed not only on one animal, but also on different animals. For example, if you perform neurovascular anastenosis in two dogs on the carotid zone (branching of the arch of the carotid artery), then you can identify the role of different parts of the central nervous system in the regulation of respiration, hematopoiesis, and vascular tone. In this case, the mode of inhaled air is changed in the bottom dog, and the regulation is seen in the other.
Transplantation of various organs. Replantation and removal of organs or various parts of the brain (extirpation). As a result of the removal of an organ, hypofunction of one or another gland is created; as a result of replanting, a situation of hyperfunction or excess of hormones of one or another gland is created.

Extirpation of various parts of the brain and cerebral cortex reveals the functions of these parts. For example, when the cerebellum was removed, its role in regulating movement, maintaining posture, and statokinetic reflexes was revealed.

Removing different areas of the cerebral cortex allowed Brodman to map the brain. He divided the cortex into 52 fields according to functional areas.

Method of transection of the brain spinal cord. Allows us to identify the functional significance of each department of the central nervous system in the regulation of somatic and visceral functions of the body, as well as in the regulation of behavior.

Implantation of electrons into various parts of the brain. Allows you to identify the activity and functional significance of a particular nervous structure in the regulation of body functions (motor functions, visceral functions and mental). Electrodes implanted into the brain are made of inert materials (that is, they must be intoxicating): platinum, silver, palladium. Electrodes make it possible not only to identify the function of a particular area, but also, on the contrary, to register in which part of the brain the appearance of a potential (VT) in response to certain functional functions. Microelectrode technology gives a person the opportunity to study the physiological foundations of the psyche and behavior.

Implantation of cannulas (micro). Perfusion is the passage of solutions of various chemical compositions through our component or the presence of metabolites in it (glucose, PVA, lactic acid) or the content of biologically active substances (hormones, neurohormones, endorphins, enkephamines, etc.). The cannula allows you to inject solutions with different contents into one or another area of ​​the brain and observe changes in functional activity from the motor system, internal organs or behavior, and psychological activity.

Microelectrode technology and conulation are used not only on animals, but also on humans during brain surgery. In most cases, this is done for diagnostic purposes.

Introduction of labeled atoms and subsequent observation on a positron emission tomograph (PET). Most often, auro-glucose labeled with gold (gold + glucose) is administered. According to Greene’s figurative expression, the universal energy donor in all living systems is ATP, and during the synthesis and resynthesis of ATP, the main energy substrate is glucose (ATP resynthesis can also occur from creatine phosphate). Therefore, the amount of glucose consumed is used to judge the functional activity of a particular part of the brain, its synthetic activity.

Glucose is consumed by cells, but gold is not utilized and accumulates in this area. The synthetic and functional activity is judged by the different active gold and its quantity.

Stereotactic methods. These are methods in which surgical operations are performed to implant electrodes in a certain area of ​​the brain in accordance with the stereotactic atlas of the brain, followed by registration of allocated fast and slow biopotentials, with registration of evoked potentials, as well as registration of EEG and myogram.

When setting new goals and objectives, the same animal can be used for a long period of observation, changing the arrangement of microelements, or perfusing various areas of the brain or organs with various solutions containing not only biologically active substances, but also metatolytes, energy substrates (glucose, creotine phosphate, ATP ).

Biochemical methods. This is a large group of techniques with the help of which the level of cations, anions, non-nonionized elements (macro and microelements), energy substances, enzymes, biologically active substances (hormones, etc.) is determined in circulating fluids, tissues, and sometimes organs. These methods are applied either in vivo (in incubators) or in tissues that continue to secrete and synthesize produced substances into the incubation medium.

Biochemical methods make it possible to assess the functional activity of a particular organ or part of it, and sometimes an entire organ system. For example, the level of 11-OCS can be used to judge the functional activity of the zona fasciculata of the adrenal cortex, but the level of 11-OCS can also be used to judge the functional activity of the hypothalamic-pituitary-adrenal system. In general, since 11-OX is the end product of the peripheral part of the adrenal cortex.

Methods for studying the physiology of GNI. The mental work of the brain has long remained inaccessible to natural science in general and to physiology in particular. Mainly because she was judged by feelings and impressions, i.e. using subjective methods. Success in this area of ​​knowledge was determined when mental activity (MAP) began to be judged using the objective method of conditioned reflexes of varying complexity of development. At the beginning of the 20th century, Pavlov developed and proposed a method for developing conditioned reflexes. Based on this technique, additional methods for studying the properties of VNI and the localization of VNI processes in the brain are possible. Of all the techniques, the most commonly used are the following:

Testing the possibility of forming different forms of conditioned reflexes (to the pitch of a sound, to a color, etc.), which allows us to judge the conditions of primary perception. Comparison of these boundaries in animals of different species makes it possible to reveal in what direction the evolution of the sensory systems of the internal nervous system went.

Ontogenetic study of conditioned reflexes. When studying the complex behavior of animals of different ages, it is possible to establish what in this behavior is innate and what is acquired. For example, Pavlov took puppies of the same litter and fed some with meat and others with milk. Upon reaching adulthood, he developed conditioned reflexes in them, and it turned out that in those dogs that received milk from childhood, conditioned reflexes were developed to milk, and in those dogs that were fed meat from childhood, conditioned reflexes were easily developed to meat. Thus, dogs do not have a strict preference for the type of carnivorous food, the main thing is that it is complete.

Phylogenetic study of conditioned reflexes. By comparing the properties of the conditioned reflex activity of animals at different levels of development, one can judge in what direction the evolution of GNI is going. For example, it turned out that the rate of formation of conditioned reflexes varies sharply from invertebrates and vertebrates, changes relatively slightly throughout the entire history of the development of vertebrates and abruptly reaches a person’s ability to immediately associate coincident events (imprinting), imprinting is also characteristic of brood birds (ducklings hatched from eggs can follow any object: a chicken, a person, and even a moving toy.The transitions between invertebrate animals - vertebrate animals, vertebrate animals - humans reflected the turning points of evolution associated with the emergence and development of VND (in insects the nervous system is of a noncellular type, in coelenterates - of a reticular type , in vertebrates - tubular type, in birds ballistic ganglia appear, some cause a high development of conditioned reflex activity. In humans, the cerebral cortex is well developed, which causes racing.

Ecological study of conditioned reflexes. The action potential that arises in the nerve cells involved in the formation of reflex connections makes it possible to identify the main links of the conditioned reflex.

It is especially important that bioelectronic indicators make it possible to observe the formation of a conditioned reflex in the structures of the brain even before it appears in the motor or autonomic (visceral) reflexes of the body. Direct stimulation of the nervous structures of the brain makes it possible to carry out model experiments on the formation of nerve connections between artificial foci of excitation. It is also possible to directly determine how the excitability of the neural structures involved in it changes during a conditioned reflex.

Pharmacological action in the formation or alteration of conditioned reflexes. By introducing certain substances into the brain, it is possible to determine what effect they have on the speed and strength of the formation of conditioned reflexes, on the ability to remake the conditioned reflex, which makes it possible to judge the functional mobility of the central nervous system, as well as on the functional state of cortical neurons and their performance. For example, it was found that caffeine ensures the formation of conditioned reflexes when the performance of nerve cells is high, and when their performance is low, even a small dose of caffeine makes excitation unbearable for the nerve cells.

Creation of an experimental pathology of conditioned reflex activity. For example, surgical removal of the temporal lobes of the cerebral cortex leads to mental deafness. The extirpation method reveals the functional significance of areas of the cortex, subcortex and brain stem. In the same way, the localization of the cortical ends of the analyzers is determined.

Modeling of processes of conditioned reflex activity. Pavlov also involved mathematicians in order to express with a formula the quantitative dependence of the formation of a conditioned reflex on the frequency of its reinforcement. It turned out that in most healthy animals, including humans, the conditioned reflex was developed in healthy people after 5 reinforcements with an unconditioned stimulus. This is especially important in service dog breeding and in the circus.

Comparison of psychological and physiological manifestations of the conditioned reflex. Support voluntary attention, flight, learning efficiency.

Comparison of psychological and physiological manifestations with bioelements and morphological with biokinetic: production of memory proteins (S-100) or areas of biologically active substances in the formation of conditioned reflexes. It has been proven that if vasopression is introduced, conditioned reflexes are developed faster (vasopression is a neuro-hormone produced in the hypothalamus). Morphological changes in the structure of a neuron: a naked neuron at birth and with denurites in an adult.
Laboratory lesson No. 1