Electrical heterogeneity of the heart. Myocardial contractility

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In cases where charge separation occurs and positive charges are located in one place and negative charges in another, physicists talk about charge polarization. Physicists use the term by analogy with different names magnetic forces, which accumulate at opposite ends, or poles (the name is given because the freely moving magnetized strip points its ends to the sides geographic poles) strip magnet.

In the case under discussion, we have a concentration of positive charges on one side of the membrane and a concentration negative charges on the other side of the membrane, that is, we can talk about a polarized membrane.

However, in any case where charge separation occurs, an electric potential immediately arises. Potential is a measure of the force that tends to bring separated charges closer together and eliminate polarization. Electric potential is therefore also called electromotive force, which is abbreviated as emf.

Electric potential is called potential precisely because it does not actually move charges, since there is an opposing force that keeps opposite electric charges from approaching each other. This force will exist as long as energy is spent to maintain it (which is what happens in cells). Thus, the force tending to bring charges together has only the ability, or potency, to do so, and such approach occurs only when the energy expended in separating the charges is weakened. Electrical potential is measured in units called volts, after Voltas, the man who created the world's first electric battery.

Physicists have been able to measure the electrical potential that exists between the two sides of the cell membrane. It turned out to be equal to 0.07 volts. We can also say that this potential is 70 millivolts, since a millivolt is equal to one thousandth of a volt. Of course it's very little potential compared to 120 volts (120,000 millivolts) mains voltage alternating current or compared to thousands of volts of voltage in power lines. But it's still an amazing potential, given the materials a cell has at its disposal to build electrical systems.

Any reason that interrupts the activity of the sodium pump will lead to a sharp equalization of the concentrations of sodium and potassium ions on both sides of the membrane. This, in turn, will automatically lead to equalization of charges. Thus, the membrane will become depolarized. Of course, this happens when the cell is damaged or dies. But there are, however, three types of stimuli that can cause depolarization without causing any harm to the cell (unless, of course, these stimuli are too strong). These lamps include mechanical, chemical and electrical.

Pressure is an example of a mechanical stimulus. Pressure on a section of the membrane causes expansion and (for reasons not yet known) will cause depolarization at that location. Heat leads to expansion of the membrane, cold contracts it, and these mechanical changes also cause depolarization.

The same result is achieved by exposing the membrane to certain chemical compounds and to weak electric currents.

(In the latter case, the cause of depolarization seems most obvious. After all, why cannot the electrical phenomenon of polarization be changed by an externally applied electrical potential?)

Depolarization that occurs in one place of the membrane serves as a stimulus for depolarization to spread across the membrane. The sodium ion, which rushes into the cell at the place where depolarization has occurred and the action of the sodium pump has ceased, displaces the potassium ion out. Sodium ions smaller in size and are more mobile than potassium ions. Therefore, more sodium ions enter the cell than potassium ions leave it. As a result, the depolarization curve crosses the zero mark and rises higher. The cell again turns out to be polarized, but with the opposite sign. At some point, the flare acquires an internal positive charge due to the presence of excess sodium ions in it. On outside a small negative charge appears on the membrane.

Opposite polarization can serve as an electrical stimulus that paralyzes the sodium pump in areas adjacent to the site of the original stimulus. These adjacent areas are polarized, then polarization occurs with the opposite sign and depolarization occurs in more distant areas. Thus, a wave of depolarization sweeps across the entire membrane. In the initial section, polarization with the opposite sign cannot last long. Potassium ions continue to leave the cell, gradually their flow equalizes the flow of incoming sodium ions. The positive charge inside the cell disappears. This disappearance of the reverse potential reactivates to some extent the sodium pump at this location in the membrane. Sodium ions begin to leave the cell, and potassium ions begin to penetrate into it. This section of the membrane enters the repolarization phase. Since these events occur in all areas of membrane depolarization, following the depolarization wave, a repolarization wave sweeps across the membrane.

Between the moments of depolarization and complete repolarization, the membranes do not respond to normal stimuli. This period of time is called the refractory period. It lasts for a very short time, a small fraction of a second. A depolarization wave passing through a certain area of the membrane makes this area immune to excitation. The previous stimulus becomes, in a sense, singular and isolated. How exactly the smallest changes in charges involved in depolarization realize such a response is unknown, but the fact remains that the membrane’s response to a stimulus is isolated and single. If a muscle is stimulated in one place with a small electrical discharge, the muscle will contract. But not only the area to which the electrical stimulation was applied will shrink; all muscle fibers will contract. The wave of depolarization travels along the muscle fiber at a speed of 0.5 to 3 meters per second, depending on the length of the fiber, and this speed is sufficient to create the impression that the muscle is contracting as one whole.

This phenomenon of polarization-depolarization-repolarization is inherent in all cells, but in some it is more pronounced. In the process of evolution, cells appeared that benefited from this phenomenon. This specialization can go in two directions. First, and this happens very rarely, organs can develop that are capable of creating high electrical potentials. When stimulated, depolarization is realized not by muscle contraction or other physiological response, but by the appearance of an electrical current. This is not a waste of energy. If the stimulus is an enemy attack, the electrical discharge can injure or kill him.

There are seven species of fish (some of them bony, some of them belong to the cartilaginous order, being relatives of sharks), specialized in this direction. The most picturesque representative is the fish, which is popularly called the “electric eel”, and in science it has a very symbolic name - Electrophorus electricus. The electric eel is a freshwater inhabitant and is found in the northern part of South America- in the Orinoco, Amazon and its tributaries. Strictly speaking, this fish is not related to eels, but was named for its long tail, which makes up four-fifths of the body of this animal, which is from 6 to 9 feet long. All the normal organs of this fish fit into the front part of the body, which is about 15 to 16 inches long.

More than half of the long tail is occupied by a series of blocks of modified muscles that form an "electric organ". Each of these muscles produces a potential that is no greater than that of a normal muscle. But thousands and thousands of elements of this “battery” are connected in such a way that their potentials add up. A rested electric eel is capable of accumulating a potential of about 600 - 700 volts and discharging it at a rate of 300 times per second. When tired, this rate drops to 50 times per second, but the eel can withstand this rate for a long time. Electric shock strong enough to kill the small animals on which this fish feeds, or to inflict a sensitive defeat on a larger animal that suddenly decides to eat the electric eel by mistake.

The electric organ is a magnificent weapon. Perhaps other animals would gladly resort to such an electric shock, but this battery takes up too much space. Imagine how few animals would have strong teeth and claws if they took up half their body weight.

The second type of specialization, involving the use of electrical phenomena occurring in cell membrane, is not to increase the potential, but to increase the speed of propagation of the depolarization wave. Cells with elongated processes appear, which are almost exclusively membranous formations. Main function these cells - very fast transmission of stimulus from one part of the body to another. It is from such cells that nerves are made - the same nerves with which this chapter began.

MF changes occur not only directly at the points of application of the cathode and anode to the nerve fiber, but also at some distance from them, but the magnitude of these shifts decreases with distance from the electrodes. Changes in MF under the electrodes are called electrotonic (kat-electroton and an-electroton, respectively), and behind the electrodes - perielectrotonic (kat- and an-perieelectroton).

An increase in MF under the anode (passive hyperpolarization) is not accompanied by a change in the ionic permeability of the membrane, even at a high applied current. Therefore, when a direct current is closed, excitation does not occur under the anode. In contrast, a decrease in the MF under the cathode (passive depolarization) entails a short-term increase in Na permeability, which leads to excitation.

The increase in membrane permeability to Na upon threshold stimulation does not immediately reach its maximum value. At the first moment, depolarization of the membrane under the cathode leads to a slight increase in sodium permeability and the opening of a small number of channels. When, under the influence of this, positively charged Na+ ions begin to enter the protoplasm, the depolarization of the membrane increases. This leads to the opening of other Na channels, and, consequently, to further depolarization, which, in turn, causes an even greater increase in sodium permeability. This circular process, based on the so-called. positive feedback, called regenerative depolarization. It occurs only when Eo decreases to a critical level (Ek). The reason for the increase in sodium permeability during depolarization is probably due to the removal of Ca++ from the sodium gate when electronegativity occurs (or electropositivity decreases) on the outer side of the membrane.

The increased sodium permeability stops after tenths of a millisecond due to sodium inactivation mechanisms.

The rate at which membrane depolarization occurs depends on the strength of the irritating current. At weak strength, depolarization develops slowly, and therefore, for an AP to occur, such a stimulus must have a long duration.

The local response that occurs with subthreshold stimuli, like AP, is caused by an increase in sodium permeability of the membrane. However, under a threshold stimulus, this increase is not large enough to cause a process of regenerative depolarization of the membrane. Therefore, the onset of depolarization is stopped by inactivation and an increase in potassium permeability.

To summarize the above, we can in the following way depict a chain of events developing in a nervous or muscle fiber under the cathode of the irritating current: passive depolarization of the membrane ---- increase sodium permeability ---gain Na flow into the fiber --- active membrane depolarization -- local response --- excess Ec --- regenerative depolarization --- action potential (AP).

What is the mechanism for the occurrence of excitation under the anode during opening? At the moment the current is turned on under the anode, the membrane potential increases - hyperpolarization occurs. At the same time, the difference between Eo and Ek grows, and in order to shift the MP to a critical level, greater force is needed. When the current is turned off (opening), the original level of Eo is restored. It would seem that at this time there are no conditions for the occurrence of excitement. But this is only true if the current lasted a very short time (less than 100 ms). With prolonged exposure to current, the critical level of depolarization itself begins to change - it grows. And finally, a moment arises when the new Ek becomes equal to the old level Eo. Now, when the current is turned off, conditions for excitation arise, because the membrane potential becomes equal to the new critical level of depolarization. The PD value when opening is always greater than when closing.

Dependence of the threshold strength of a stimulus on its duration. As already indicated, the threshold strength of any stimulus, within certain limits, is inversely related to its duration. This dependence manifests itself in a particularly clear form when rectangular direct current shocks are used as a stimulus. The curve obtained in such experiments was called the “force-time curve.” It was studied by Goorweg, Weiss and Lapik at the beginning of the century. From an examination of this curve, it follows first of all that a current below a certain minimum value or voltage does not cause excitation, no matter how long it lasts. The minimum current strength capable of causing excitation is called rheobase by Lapik. The shortest time during which an irritating stimulus must act is called useful time. Increasing the current leads to a shortening of the minimum stimulation time, but not indefinitely. With very short stimuli, the force-time curve becomes parallel to the coordinate axis. This means that with such short-term irritations, excitation does not occur, no matter how great the strength of irritation.

Determining useful time is practically difficult, since the point of useful time is located on a section of the curve that turns into parallel. Therefore, Lapik suggested using useful time two rheobases - chronaxy. Its point is located on the steepest part of the Goorweg-Weiss curve. Chronaximetry has become widespread both experimentally and clinically for diagnosing damage to motor nerve fibers.

It was already indicated above that depolarization of the membrane leads to the onset of two processes: one fast, leading to an increase in sodium permeability and the occurrence of AP, and the other slow, leading to inactivation of sodium permeability and the end of excitation. With a steep increase in stimulus, Na activation has time to reach a significant value before Na inactivation develops. In the case of a slow increase in current intensity, inactivation processes come to the fore, leading to an increase in the threshold and a decrease in the AP amplitude. All agents that enhance or accelerate inactivation increase the rate of accommodation.

Accommodation develops not only with irritation of excitable tissues electric shock, but also in the case of the use of mechanical, thermal and other stimuli. Thus, a quick blow to a nerve with a stick causes its excitation, but when slowly pressing on the nerve with the same stick, no excitation occurs. An isolated nerve fiber can be excited by rapid cooling, but not by slow cooling. A frog will jump out if it is thrown into water with a temperature of 40 degrees, but if the same frog is placed in cold water, and heat it slowly, then the animal will be cooked, but will not react by jumping to the rise in temperature.

In the laboratory, an indicator of the speed of accommodation is the smallest slope of the current increase at which the stimulus still retains the ability to cause AP. This minimum slope is called the critical slope. It is expressed either in absolute units (mA/sec) or in relative ones (as the ratio of the threshold strength of that gradually increasing current, which is still capable of causing excitation, to the rheobase of a rectangular current impulse).

Figure 4. Goorweg-Weiss force-time curve. Designations: X - chronaxy, PV - useful time, P - rheobase, 2р - force of two rheobases

The "all or nothing" law. When studying the dependence of the effects of stimulation on the strength of the applied stimulus, the so-called "all or nothing" law.

According to this law, under threshold stimuli they do not cause excitation ("nothing"), but under threshold stimuli, excitation immediately acquires a maximum value ("all"), and no longer increases with further intensification of the stimulus.

This pattern was initially discovered by Bowditch while studying the heart, and was later confirmed in other excitable tissues. For a long time the all-or-nothing law has been incorrectly interpreted as general principle response of excitable tissues. It was assumed that “nothing” meant a complete absence of response to a subthreshold stimulus, and “everything” was considered as a manifestation of the complete exhaustion of the excitable substrate’s potential capabilities. Further studies, especially microelectrode studies, showed that this point of view is not true. It turned out that at subthreshold forces, local non-propagating excitation (local response) occurs. At the same time, it turned out that “everything” also does not characterize the maximum that PD can achieve. In a living cell, there are processes that actively stop membrane depolarization. If the incoming Na current, which ensures the generation of AP, is weakened by any influence on the nerve fiber, for example, drugs, poisons, then it ceases to obey the “all or nothing” rule - its amplitude begins to gradually depend on the strength of the stimulus. Therefore, “all or nothing” is now considered not as a universal law of the response of an excitable substrate to a stimulus, but only as a rule, characterizing the features of the occurrence of AP in given specific conditions.

The concept of excitability. Changes in excitability when excited. Excitability parameters.

Excitability is the ability of a nerve or muscle cell to respond to stimulation by generating PD. The main measure of excitability is usually rheobase. The lower it is, the higher the excitability, and vice versa. This is due to the fact that, as we said earlier, the main condition for the occurrence of excitation is the achievement of a critical level of depolarization by the MF (Eo<= Ек). Поэтому мерилом возбудимости является разница между этими величинами (Ео - Ек). Чем меньше эта разница, тем меньшую силу надо приложить к клетке, чтобы сдвинуть мембранный потенциал до критического уровня, и, следовательно, тем больше возбудимость клетки.

Pflueger also showed that excitability is a variable quantity. The cathode increases excitability, the anode decreases it. Let us recall that these changes in excitability under the electrodes are called electrotonic. The Russian scientist Verigo showed that with prolonged exposure to direct current on the tissue, or under the influence of strong stimuli, these electrotonic changes in excitability are perverted - under the cathode, the initial increase in excitability is replaced by its decrease (the so-called cathodic depression develops), and under the anode, the reduced excitability gradually increases . The reason for these changes in excitability at the DC poles is due to the fact that the value of Ek changes with prolonged exposure to the stimulus. Under the cathode (and during excitation), Ek gradually moves away from the MP and decreases, so that a moment comes when the difference E0-Ek becomes greater than the initial one. This leads to a decrease in tissue excitability. On the contrary, under the anode Ek tends to increase, gradually approaching Eo. In this case, excitability increases, as the initial difference between Eo and Ek decreases.

The reason for the change in the critical level of depolarization under the cathode is the inactivation of sodium permeability due to prolonged depolarization of the membrane. At the same time, permeability to K increases significantly. All this leads to the fact that the cell membrane loses its ability to respond to irritating stimuli. The same changes in the membrane underlie the already discussed phenomenon of accommodation. Under the anode, under the action of current, the inactivation phenomena are reduced.

Changes in excitability when excited. The occurrence of AP in a nerve or muscle fiber is accompanied by multiphase changes in excitability. To study them, a nerve or muscle is exposed to two short electrical stimuli following each other at a certain interval. The first is called annoying, the second - testing. Registration of PDs arising in response to these irritations made it possible to establish important facts.

Figure 5. Changes in excitability during arousal.

Designations: 1- increased excitability during a local response; 2 – absolute refractoriness; 3- relative refractoriness; 4- supernormal excitability during trace depolarization; 5 – subnormal excitability during trace hyperpolarization.

During a local response, excitability is increased, since the membrane is depolarized and the difference between E0 and Ek falls. The period of occurrence and development of the peak of the action potential corresponds to the complete disappearance of excitability, called absolute refractoriness (unimpressibility). At this time, the testing stimulus is not capable of causing a new AP, no matter how strong this irritation is. The duration of absolute refractoriness approximately coincides with the duration of the ascending branch of AP. In fast-conducting nerve fibers it is 0.4-0.7 ms. In the fibers of the heart muscle - 250-300 ms. Following absolute refractoriness, the phase of relative refractoriness begins, which lasts 4-8 ms. It coincides with the AP repolarization phase. At this time, excitability gradually returns to its original level. During this period, the nerve fiber is able to respond to strong stimulation, but the amplitude of the action potential will be sharply reduced.

According to the Hodgkin-Huxley ion theory, absolute refractoriness is caused first by the presence of maximum sodium permeability, when a new stimulus cannot change or add anything, and then by the development of sodium inactivation, which closes Na channels. This is followed by a decrease in sodium inactivation, as a result of which the ability of the fiber to generate AP is gradually restored. This is a state of relative refractoriness.

The relative refractory phase is replaced by a phase of increased (supernormal) excitability And, coinciding in time with the period of trace depolarization. At this time, the difference between Eo and Ek is lower than the original one. In motor nerve fibers of warm-blooded animals, the duration of the supernormal phase is 12-30 ms.

The period of increased excitability is replaced by a subnormal phase, which coincides with trace hyperpolarization. At this time, the difference between the membrane potential (Eo) and the critical level of depolarization (Ek) increases. The duration of this phase is several tens or hundreds of ms.

Lability. We examined the basic mechanisms of the occurrence and propagation of a single excitation wave in nerve and muscle fibers. However, in the natural conditions of an organism’s existence, not single, but rhythmic volleys of action potentials pass through nerve fibers. In sensitive nerve endings located in any tissue, rhythmic discharges of impulses arise and spread along the afferent nerve fibers extending from them, even with very short-term stimulation. Likewise, from the central nervous system along the efferent nerves there is a flow of impulses to the periphery to the executive organs. If the executive organ is skeletal muscles, then flashes of excitation occur in them in the rhythm of impulses arriving along the nerve.

The frequency of impulse discharges in excitable tissues can vary widely depending on the strength of the applied stimulation, the properties and condition of the tissue, and the speed of individual acts of excitation in a rhythmic series. To characterize this speed, the concept of lability was formulated. By lability, or functional mobility, he understood a greater or lesser rate of occurrence of those elementary reactions that accompany excitation. A measure of lability is the largest number of action potentials that an excitable substrate is capable of reproducing per unit time in accordance with the frequency of applied stimulation.

Initially it was assumed that the minimum interval between impulses in a rhythmic series should correspond to the duration of the absolute refractory period. Precise studies, however, have shown that with a repetition rate of stimuli with such an interval, only two impulses arise, and the third drops out due to developing depression. Therefore, the interval between pulses should be slightly greater than the absolute refractory period. In the motor nerve cells of warm-blooded animals, the refractory period is about 0.4 msec, and the potential maximum rhythm should be equal to 2500/sec, but in fact it is about 1000/sec. It should be emphasized that this frequency significantly exceeds the frequency of impulses passing through these fibers under physiological conditions. The latter is about 100/sec.

The fact is that usually in natural conditions the tissue works with the so-called optimal rhythm. To transmit impulses with such a rhythm, a great force of stimulation is not required. Studies have shown that the frequency of stimulation and the rheobase of the current capable of causing nerve impulses with such a frequency are in a peculiar relationship: the rheobase first drops as the frequency of the impulses increases, then increases again. The optimum is for nerves in the range from 75 to 150 pulses/sec, for muscles - 20-50 pulses/sec. This rhythm, unlike others, can be reproduced very persistently and for a long time by excitable formations.

Thus, we can now name all the main parameters of tissue excitability that characterize its properties: rheobase, useful time (chronaxy), critical slope, lability. All of them, except the last one, are in inversely proportional relationships with excitability.

The concept of "parabiosis". Lability is a variable value. It can change depending on the state of the nerve or muscle, depending on the strength and duration of the irritations falling on them, on the degree of fatigue, etc. For the first time, I studied the change in the lability of a nerve when it is exposed to first chemical and then electrical stimuli. He discovered a natural decrease in the lability of a nerve section altered by a chemical agent (ammonia), called this phenomenon “parabiosis” and studied its patterns. Parabiosis is a reversible condition, which, however, with the deepening of the action of the agent causing it, can become irreversible.

Vvedensky considered parabiosis as a special state of persistent, unfluctuating excitation, as if frozen in one section of the nerve fiber. Indeed, the parabiotic site is negatively charged. Vvedensky considered this phenomenon to be a prototype of the transition of excitation to inhibition in nerve centers. In his opinion, parabiosis is the result of overexcitation of a nerve cell by too much or too frequent stimulation.

The development of parabiosis occurs in three stages: equalizing, paradoxical and inhibitory. Initially, due to a decrease in accommodation, individual current pulses of low frequency, provided they are of sufficient strength, no longer produce 1 pulse, but 2,3 or even 4. At the same time, the threshold of excitability increases, and the maximum rhythm of excitation progressively decreases. As a result, the nerve begins to respond to impulses of both low and high frequencies with the same frequency of discharges, which is closest to the optimal rhythm for this nerve. This is the equalizing phase of parabiosis. At the next stage of development of the process, in the region of threshold intensities of stimulation, the reproduction of a rhythm close to optimal is still preserved, and the tissue either does not respond to frequent impulses at all, or responds with very rare waves of excitation. This is a paradoxical phase.

Then the fiber’s ability to perform rhythmic wave activity decreases, the amplitude of the AP also decreases, and its duration increases. Any external influence reinforces the state of inhibition of the nerve fiber and at the same time inhibits itself. This is the last, inhibitory phase of parabiosis.

Currently, the described phenomenon is explained from the perspective of the membrane theory by a violation of the mechanism of increasing sodium permeability and the appearance of prolonged sodium inactivation. As a result of this, Na channels remain closed; it accumulates in the cell and the outer surface of the membrane long time retains a negative charge. This prevents new irritation by lengthening the refractory period. When approaching a site of parabiosis with frequently successive APs, the inactivation of sodium permeability caused by the altering agent is added to the inactivation that accompanies the nerve impulse. As a result, excitability is reduced so much that the conduction of the next impulse is completely blocked.

Metabolism and energy during excitement. When excitation occurs and occurs in nerve cells and muscle fibers, metabolism increases. This is manifested both in a number of biochemical changes occurring in the membrane and protoplasm of cells, and in an increase in their heat production. It has been established that when excited, the following occurs: increased breakdown in cells of energy-rich compounds - ATP and creatine phosphate (CP), increased processes of breakdown and synthesis of carbohydrates, proteins and lipids, increased oxidative processes, leading in combination with glycolysis to the resynthesis of ATP and CP, synthesis and destruction of acetylcholine and norepinephrine, other mediators, increased synthesis of RNA and proteins. All these processes are most pronounced during the period of restoration of the membrane state after PD.

In nerves and muscles, each wave of excitation is accompanied by the release of two portions of heat, of which the first is called initial, and the second - delayed heat. Initial heat generation occurs at the moment of excitation and constitutes an insignificant part of the total heat production (2-10%) during excitation. It is assumed that this heat is associated with those physicochemical processes that develop at the moment of generation of PD. Delayed heat generation occurs over a longer period of time, lasting many minutes. It is associated with those chemical processes that occur in the tissue following a wave of excitation, and, in the figurative expression of Ukhtomsky, constitute the “metabolic tail of the comet of excitation.”

Carrying out stimulation. Classification of nerve fibers.

As soon as an AP occurs at any point in a nerve or muscle fiber and this area acquires a negative charge, an electric current arises between the excited and neighboring resting sections of the fiber. In this case, the excited section of the membrane acts on neighboring sections as a direct current cathode, causing their depolarization and generating a local response. If the magnitude of the local response exceeds the Ec of the membrane, PD occurs. As a result, the outer surface of the membrane becomes negatively charged in the new area. In this way, the excitation wave propagates along the entire fiber at a speed of about 0.5-3 m/sec.

Laws of conduction of excitation along nerves.

1. The law of physiological continuity. Cutting, ligating, as well as any other impact that disrupts the integrity of the membrane (physiological, and not just anatomical), creates non-conductivity. The same thing occurs with thermal and chemical influences.

2. Law of bilateral conduction. When irritation is applied to a nerve fiber, excitation spreads along it in both directions (along the surface of the membrane - in all directions) at the same speed. This is proven by the experience of Babukhin and others like him.

3. Law of isolated conduction. In a nerve, impulses propagate along each fiber in isolation, that is, they do not pass from one fiber to another. This is very important as it ensures precise addressing of the pulse. This is due to the fact that the electrical resistance of the myelin and Schwann sheaths, as well as the intercellular fluid, is much greater than the resistance of the nerve fiber membrane.

The mechanisms and speed of excitation in the non-pulpal and pulpal nerve fibers are different. In the pulpless excitation spreads continuously along the entire membrane from one excited area to another located nearby, as we have already discussed.

In myelin fibers, excitation spreads only spasmodically, jumping over areas covered with the myelin sheath (saltatory). Action potentials in these fibers arise only at the nodes of Ranvier. At rest, the outer surface of the excitable membrane of all nodes of Ranvier is positively charged. At the moment of excitation, the surface of the first interception becomes negatively charged with respect to the adjacent second interception. This leads to the emergence of a local electric current that flows through the intercellular fluid, membrane and axoplasm surrounding the fiber from interception 2 to 1. The current emerging through interception 2 excites it, causing the membrane to recharge. Now this area can excite the next one, etc.

Jumping of the AP over the interinterceptual area is possible because the amplitude of the AP is 5-6 times greater than the threshold required to excite not only the next one, but also 3-5 interceptions. Therefore, microdamage to the fiber in the interinterceptor areas or in more than one interception does not stop the functioning of the nerve fiber until the regenerative phenomena involve 3 or more adjacent Schwann cells.

The time required for the transfer of excitation from one interception to another is the same for fibers of different diameters, and is 0.07 ms. However, since the length of the interstitial sections is different and proportional to the diameter of the fiber, in myelinated nerves the speed of nerve impulses is directly proportional to their diameter.

Classification of nerve fibers. The electrical response of an entire nerve is the algebraic sum of the PD of its individual nerve fibers. Therefore, on the one hand, the amplitude of the electrical impulses of the whole nerve depends on the strength of the stimulus (as it increases, more and more fibers are involved), and secondly, the total action potential of the nerve can be divided into several separate oscillations, the reason for which is the unequal speed of impulse conduction along the nerve. different fibers that make up the whole nerve.

At present, nerve fibers are usually divided into three main types based on the speed of excitation, the duration of various phases of action activity, and structure.

Type A fibers are divided into subgroups (alpha, beta, gamma, delta). They are covered with a myelin sheath. Their conduction speed is the highest - 70-120 m/sec. These are motor fibers from the motor neurons of the spinal cord. The remaining type A fibers are sensitive.

Type B fibers are myelinated, predominantly preganglionic. Conduction speed - 3-18 m/sec.

Type C fibers are pulpless, with a very small diameter (2 microns). The speed of conduction is no more than 3 m/sec. These are most often postganglionic fibers of the sympathetic nervous system.

GENERAL PHYSIOLOGY

CENTRAL NERVOUS SYSTEM

The physiology of the central nervous system (CNS) is the most complex, but at the same time the most responsible chapter of physiology, since in higher mammals and humans the nervous system performs the function of connecting parts of the body with each other, their relationship and integration, on the one hand, and the function connections between environmental agents and certain manifestations of the body’s activity, on the other. The successes of modern science in deciphering the entire complexity of the nervous system are based on the recognition of a single mechanism of its functioning - the reflex.

Reflexes are all acts of the body that occur in response to irritation of receptors and are carried out with the participation of the central nervous system. The idea of a reflex was first formulated by Descartes and developed by Sechenov, Pavlov, and Anokhin. Each reflex is carried out thanks to the activity of certain structural formations of the nervous system. However, before we analyze the structural features of the reflex arc, we must get acquainted with the structure and properties of the functional unit of the nervous system - the nerve cell, neuron.

Structure and functions of a neuron. Back in the last century, Ramon y Cajal discovered that any nerve cell has a body (soma) and processes, which, according to structural features and function, are divided into dendrites and axons. A neuron always has only one axon, but there can be a lot of dendrites. In 1907, Sherrington described the ways neurons interact with each other and introduced the concept of synapse. After Ramon y Cajal showed that dendrites perceive stimulation and the axon sends impulses, the idea was formed that the main function of a neuron is perception. processing and sending information to another nerve cell or to a working organ (muscle, gland).

The structure and size of neurons vary greatly. Their diameter can range from 4 microns (cerebellar granule cells) to 130 microns (Betz giant pyramidal cells). The shape of neurons is also varied.

Nerve cells have very large nuclei that are functionally and structurally connected to the cell membrane. Some neurons are multinucleated, for example, neurosecretory cells of the hypothalamus or during neuronal regeneration. In the early postnatal period, neurons can divide.

In the cytoplasm of the neuron the so-called Nissl's substance is a granule of the endoplasmic reticulum rich in ribosomes. There is a lot of it around the core. Under the cell membrane, the endoplasmic reticulum forms cisterns responsible for maintaining the K+ concentration under the membrane. Ribosomes are colossal protein factories. The entire protein of a nerve cell is renewed in 3 days, and even faster when the function of the neuron increases. The agranular reticulum is represented by the Golgi apparatus, which seems to surround the entire nerve cell from the inside. It contains lysosomes containing various enzymes and vesicles with mediator granules. The Golgi apparatus takes an active part in the formation of vesicles with the mediator.

Both in the cell body and in the processes there are many mitochondria, the energy stations of the cell. These are mobile organelles that, due to actomyosin, can move to where energy is needed in the cell for its activity.

During an action potential, the intracellular potential becomes positive, as the excited membrane temporarily becomes more permeable to Na + (compared to K +) , therefore, the membrane potential for some time approaches the equilibrium potential of sodium ions (E Na) - E Na can be determined using the Nernst ratio; at extracellular and intracellular concentrations of Na + 150 and 10 mM, respectively, it will be:

However, the increased permeability to Na + persists only for a short time, so that the membrane potential does not reach E Na and returns to the resting level after the end of the action potential.

The above changes in permeability, causing the development of the depolarization phase of the action potential, arise due to the opening and closing of special membrane channels, or pores, through which sodium ions easily pass. The gating is believed to regulate the opening and closing of individual channels, which can exist in at least three conformations - open, closed and inactivated. One gate corresponding to the activation variable " m" in the Hodgkin-Huxley description of sodium ion currents in the membrane of the squid giant axon, rapidly move to open a channel when the membrane is suddenly depolarized by a stimulus. Other gates corresponding to the inactivation variable " h"in the Hodgkin-Huxley description, during depolarization they move more slowly, and their function is to close the channel (Fig. 3.3). Both the steady-state distribution of gates within the channel system and the rate of their transition from one position to another depend on the level of membrane potential. Therefore, the terms “time-dependent” and “voltage-dependent” are used to describe membrane Na + conductance.

If the resting membrane is suddenly depolarized to a positive potential (for example, in a voltage-clamp experiment), the activation gate will quickly change its position to open the sodium channels, and then the inactivation gate will slowly close them (Figure 3.3). The word "slow" here means that inactivation takes a few milliseconds, while activation occurs in a fraction of a millisecond. The gates remain in these positions until the membrane potential changes again, and for all gates to return to their original resting state, the membrane must be completely repolarized to a high negative potential level. If the membrane is repolarized only to a low level of negative potential, then some inactivation gates will remain closed and the maximum number of available sodium channels that can open upon subsequent depolarization will be reduced. (The electrical activity of cardiac cells in which sodium channels are completely inactivated will be discussed below.) Complete repolarization of the membrane at the end of a normal action potential ensures that all gates return to their original state and are therefore ready for the next action potential.

Rice. 3.3. Schematic representation of membrane channels for inward ion flows at the resting potential, as well as during activation and inactivation.

On the left is the sequence of channel states at a normal resting potential of -90 mV. At rest, the inactivation gates of both the Na + channel (h) and the slow Ca 2+ /Na + channel (f) are open. During activation upon excitation of the cell, the t-gate of the Na + channel opens and the incoming flow of Na + ions depolarizes the cell, which leads to an increase in the action potential (graph below). The h-gate then closes, thus inactivating Na+ conduction. As the action potential rises, the membrane potential exceeds the more positive threshold of the slow channel potential; their activation gate (d) opens and Ca 2+ and Na + ions enter the cell, causing the development of the plateau phase of the action potential. Gate f, which inactivates Ca 2+ /Na + channels, closes much more slowly than gate h, which inactivates Na channels. The central fragment shows the behavior of the channel when the resting potential decreases to less than -60 mV. Most Na channel inactivation gates remain closed as long as the membrane is depolarized; The incoming flow of Na+ that occurs when the cell is stimulated is too small to cause the development of an action potential. However, the inactivation gate (f) of the slow channels does not close and, as shown in the fragment on the right, if the cell is sufficiently excited to open the slow channels and allow slowly incoming ion flows to pass, a slow development of an action potential is possible in response.

Rice. 3.4. Threshold potential for cardiac cell excitation.

On the left is the action potential occurring at the resting potential level of -90 mV; this occurs when the cell is excited by an incoming impulse or some subthreshold stimulus that quickly lowers the membrane potential to values below the threshold level of -65 mV. On the right are the effects of two subthreshold and threshold stimuli. Subthreshold stimuli (a and b) do not reduce the membrane potential to the threshold level; therefore, no action potential occurs. The threshold stimulus (c) reduces the membrane potential exactly to the threshold level, at which an action potential then occurs.

The rapid depolarization at the onset of an action potential is caused by a powerful influx of sodium ions entering the cell (corresponding to their electrochemical potential gradient) through open sodium channels. However, first of all, sodium channels must be effectively opened, which requires rapid depolarization of a sufficiently large area of the membrane to the required level, called the threshold potential (Fig. 3.4). Experimentally, this can be achieved by passing current through the membrane from an external source and using an extracellular or intracellular stimulating electrode. Under natural conditions, the same purpose is served by local currents flowing through the membrane immediately before the propagating action potential. At the threshold potential, a sufficient number of sodium channels are open, which provides the necessary amplitude of the incoming sodium current and, consequently, further depolarization of the membrane; in turn, depolarization causes more channels to open, resulting in an increase in the incoming flow of ions, so that the depolarization process becomes regenerative. The rate of regenerative depolarization (or action potential rise) depends on the strength of the incoming sodium current, which in turn is determined by factors such as the magnitude of the Na + electrochemical potential gradient and the number of available (or non-inactivated) sodium channels. In Purkinje fibers, the maximum rate of depolarization during the development of an action potential, denoted as dV/dt max or V max, reaches approximately 500 V/s, and if this rate were maintained throughout the depolarization phase from -90 mV to +30 mV, then the change a potential of 120 mV would take about 0.25 ms. The maximum depolarization rate of the fibers of the working ventricular myocardium is approximately 200 V/s, and that of the atrial muscle fibers is from 100 to 200 V/s. (The depolarization phase of the action potential in the cells of the sinus and atrioventricular nodes differs significantly from that just described and will be discussed separately; see below.)

Action potentials with such a high rate of rise (often called “fast responses”) travel rapidly throughout the heart. The speed of action potential propagation (as well as Vmax) in cells with the same membrane permeability and axial resistance characteristics is determined mainly by the amplitude of the inward current flowing during the rise phase of the action potential. This is due to the fact that the local currents passing through the cells immediately before the action potential are larger in magnitude with a faster rise in potential, so the membrane potential in these cells reaches the threshold level earlier than in the case of currents of smaller magnitude (see Fig. 3.4) . Of course, these local currents flow through the cell membrane immediately after the propagating action potential has passed, but they are no longer able to excite the membrane due to its refractoriness.

Rice. 3.5. Normal action potentials and responses evoked by stimuli at different stages of repolarization.

The amplitude and increase in rate of responses evoked during repolarization depend on the level of membrane potential at which they occur. The earliest responses (a and b) occur at such a low level that they are too weak and unable to spread (gradual or local responses). Response "c" represents the earliest of the propagating action potentials, but its propagation is slow due to the slight increase in speed as well as the low amplitude. The “d” response appears just before complete repolarization, its rate of increase and amplitude are higher than with the “c” response, since it occurs at a higher membrane potential; however, its rate of spread becomes slower than normal. The “d” response is noted after complete repolarization, therefore its amplitude and depolarization rate are normal; hence, it spreads quickly. PP - resting potential.

The low rate of rise of action potentials evoked during the relative refractory period causes their slow propagation; Such action potentials can cause several conduction disturbances, such as delay, attenuation and blocking, and can even cause excitation circulation. These phenomena are discussed later in this chapter.

In normal cardiac cells, the incoming sodium current responsible for the rapid rise of the action potential is followed by a second incoming current, smaller and slower than the sodium current, which appears to be carried primarily by calcium ions. This current is usually referred to as the "slow inward current" (although it is only such in comparison to the fast sodium current; other important changes, such as those observed during repolarization, are probably slower); it flows through channels which, due to their time- and voltage-dependent conductivity characteristics, have been called “slow channels” (see Fig. 3.3). The activation threshold for this conductance (i.e., when the activation gate d begins to open) lies between -30 and -40 mV (compare: -60 to -70 mV for sodium conductance). The regenerative depolarization caused by the fast sodium current usually activates the conduction of the slow incoming current, so that during the later rise of the action potential, current flows through both types of channels. However, the Ca 2+ current is much smaller than the maximum fast Na + current, so its contribution to the action potential is very small until the fast Na + current becomes sufficiently inactivated (i.e., after the initial rapid rise of the potential). Since the slow incoming current can only be inactivated very slowly, it contributes mainly to the plateau phase of the action potential. Thus, the plateau level shifts towards depolarization when the electrochemical potential gradient for Ca 2+ increases with increasing concentration of [Ca 2+ ] 0; a decrease in [Ca 2+ ] 0 causes a shift in the plateau level in the opposite direction. However, in some cases there may be a contribution of calcium current to the rise phase of the action potential. For example, the action potential rise curve in frog ventricular myocardial fibers sometimes exhibits a bend around 0 mV, at the point where the initial fast depolarization gives way to a slower depolarization that continues until the peak of the action potential overshoot. It has been shown that the rate of slower depolarization and the magnitude of overshoot increase with increasing [Ca 2+ ] 0 .

In addition to their different dependence on membrane potential and time, these two types of conductivity also differ in their pharmacological characteristics. Thus, the current through fast Na + channels is reduced by tetrodotoxin (TTX), while the slow Ca 2+ current is not affected by TTX, but is enhanced by catecholamines and inhibited by manganese ions, as well as some drugs such as verapamil and D- 600. It seems very likely (at least in the frog heart) that most of the calcium needed to activate the proteins that contribute to each heartbeat enters the cell during the action potential through the slow inward current channel. In mammals, an available additional source of Ca 2+ for cardiac cells is its reserves in the sarcoplasmic reticulum.

Biological membrane, Membrane thickness 7-10 nm, consists of a double layer of phospholipids: hydrophilic parts (heads) are directed towards the surface of the membrane; hydrophobic parts (tails) are directed into the membrane. Hydrophobic ends stabilize the membrane as a bilayer

FUNCTIONS OF MEMBRANES STRUCTURALSTRUCTURAL. PROTECTIVE.PROTECTIVE. ENZYMATIVEENZYMATIVE CONNECTIVE OR ADHESIVE (determines the existence of multicellular organisms). RECEPTORRECEPTOR. ANTIGENAANTIGENIC. ELECTROGENICELECTROGENICTRANSPORTANTTRANSPORT.

COMMUNICATION BETWEEN CELLS CELL signaling molecule (first messenger) or ligand CELL signaling molecule (first messenger) or ligand membrane molecule (channel or receptor) membrane molecule (channel or receptor) TARGET CLUTES cell molecules or second messengers cascade of enzymatic reactions change in cell function CLECTS -TARGET molecules of the cell or second messengers cascade of enzymatic reactions changing the function of the cell

MEMBRANE RECEPTORS These are molecules (proteins, glyco- or lipoproteins) sensitive to biologically active substances - ligands These are molecules (proteins, glyco- or lipoproteins) sensitive to biologically active substances - ligands Ligands are external stimuli for the cell Ligands are external stimuli for the cell Receptors – highly specific or selective Receptors – highly specific or selective

MECHANISM OF OPERATION OF RECEPTORS Membrane receptors detect the presence of a ligand: they transmit a signal to intracellular chemical compounds to second messengers - MESSENGERS 2. 2. Regulate the state of ion channels

PROPERTIES OF ION CHANNELS 1.Selectivity - 1.Selectivity - each channel allows only a specific (“its own”) ion to pass through. It can be in different functional states: closed, but ready to open (1) open – activated (2) Inactivated (3)

Hyperpolarization Increase in the potential difference between the sides of the membrane Increase in the difference in the potential between the sides of the membrane DEPOLARIZATION Decrease in the potential difference between the sides of the membrane Decrease in the potential difference between the sides of the membrane REPOLARIZATION Increase in the magnitude of MP after depolarization.

RESTING MEMBRANE POTENTIAL This is the potential difference between the outer and inner surfaces of the membrane of an excitable cell that is at rest. The resting potential is recorded by an intracellular microelectrode in relation to a reference extracellular electrode.

Gradient This is a vector that shows the difference between the largest and smallest value of a quantity at different points in space, and also indicates the degree of this change. This is a vector showing the difference between the largest and smallest value of a quantity at different points in space, and also indicating the degree of this change.

FACTORS FORMING MP 1. ION ASYMETRY Potassium concentration gradient Potassium concentration gradient Sodium concentration gradient Sodium concentration gradient = p = 8-10p

2. Membrane semi-permeability K + Na + Cl - Protein

“Electric gradient” This is the force created by the electric field of the transmembrane potential difference. This is the force created by the electric field of the transmembrane potential difference. The release of potassium to the outside reduces the concentration gradient, and the electric one increases it. The release of potassium to the outside reduces the concentration gradient, while the electrical gradient increases it. As a result, the magnitude of the gradients is equalized As a result, the magnitude of the gradients is equalized

“Electric gradient” A transmembrane potential difference creates an electric field, and therefore an electric gradient. A transmembrane potential difference creates an electric field, and therefore an electric gradient. As potassium comes out, the concentration gradient decreases, and the electric gradient increases. As potassium escapes, the concentration gradient decreases, and the electrical gradient increases. As a result, the two gradients become equalized As a result, two gradients become equalized

Equilibrium potential - an equilibrium state is such a value of the electrical charge of the membrane that completely balances the concentration gradient for a certain ion and the total current of this ion will be equal to 0. an equilibrium state is such a value of the electrical charge of the membrane that completely balances the concentration gradient for a certain ion and the total current of this ion will be equal to 0. Equilibrium potential for potassium = -86 mV (Ek+ = -86 mV) Equilibrium potential for potassium = -86 mV (Ek+ = -86 mV)

Resting state for the cell The membrane is slightly permeable to sodium, which reduces the charge difference and the magnitude of the electrical gradient The membrane is slightly permeable to sodium, which reduces the charge difference and the magnitude of the electrical gradient Potassium leaves the cell Potassium leaves the cell

Mechanisms for maintaining ionic asymmetry Electric charge on the membrane - promotes the entry of potassium into the cell and inhibits its exit Electric charge on the membrane - promotes the entry of potassium into the cell and inhibits its exit Potassium-sodium pump - active transport that transports ions across the membrane against the concentration gradient Potassium-sodium pump sodium pump - active transport that transports ions across the membrane against a concentration gradient

FUNCTIONS OF POTASSIUM-SODIUM PUMP Active ion transport Active ion transport ATPase enzymatic activity ATPase enzymatic activity Maintaining ion asymmetry Maintaining ion asymmetry Enhancing membrane polarization - electrogenic effect Enhancing membrane polarization - electrogenic effect

Depolarization Occurs when sodium channels open Occurs when sodium channels open Sodium enters the cell: Sodium enters the cell: decreases the negative charge on the inner surface of the membrane decreases the negative charge on the inner surface of the membrane decreases the electric field around the membrane decreases the electric field around the membrane The degree of depolarization depends on the amount open sodium channels The degree of depolarization depends on the number of open sodium channels

CRITICAL LEVEL OF DEPOLARIZATION E cr The level of depolarization at which the maximum possible number of sodium channels opens (all channels for sodium are open) The level of depolarization at which the maximum possible number of sodium channels opens (all channels for sodium are open) The flow of sodium ions “avalanche” rushes into the cell The flow of sodium ions rushes into the cell like an “avalanche.” Regenerative depolarization begins. Regenerative depolarization begins.

Depolarization threshold Difference between the value of the initial polarization of the membrane (E 0) and the critical level of depolarization (E cr) Difference between the value of the initial polarization of the membrane (E 0) and the critical level of depolarization (E cr) Δ V= E 0 - E cr Δ V= E 0 - E cr In this case, the sodium current exceeds the potassium current by 20 times! In this case, the sodium current exceeds the potassium current by 20 times! Depends on the ratio of activated sodium and potassium channels Depends on the ratio of activated sodium and potassium channels

"All or nothing" law Subthreshold stimulus causes local depolarization ("nothing") Subthreshold stimulus causes local depolarization ("nothing") Threshold stimulus causes the maximum possible response ("All") Threshold stimulus causes the maximum possible response ("All") Suprathreshold stimulus causes the same response as the threshold one. A suprathreshold stimulus causes the same response as the threshold one. the cell's response does not depend on the strength of the stimulus. That. the cell's response does not depend on the strength of the stimulus.

LO Properties of LO 1. Does not obey the “all or nothing” law Amplitude of LO depends on the strength of the stimulus Propagates across the membrane by attenuation (decrement) Can be summed (as a result, the amplitude of depolarization increases) Transforms into an action potential when the level of critical depolarization is reached

Action potential (AP) This is the potential difference between the excited and non-excited areas of the membrane, which arises as a result of rapid depolarization of the membrane followed by its recharge. This is the potential difference between the excited and non-excited sections of the membrane, which arises as a result of rapid depolarization of the membrane followed by its recharge. AP amplitude is about 120 – 130 µV, duration (on average) is 3 – 5 ms AP amplitude is about 120 – 130 µV, duration (on average) is 3 – 5 ms (in different tissues from 0.01 ms to 0.3 s) . (in different tissues from 0.01 ms to 0.3 s).

E0E0 E cr mV

Conditions for the occurrence of AP Depolarization must reach a critical level of depolarization Depolarization must reach a critical level of depolarization The sodium current into the cell must exceed the potassium current from the cell by 20 times (the channels for sodium are fast-conducting, and for potassium are slow) The sodium current into the cell must exceed the potassium current from the cell 20 times (channels for sodium are fast-conducting, and for potassium are slow) Regenerative depolarization should develop Regenerative depolarization should develop

E0E0 E cr 0 +30

Irritation This is the process of influencing the cell This is the process of influencing the cell The effect of the effect depends on both the qualitative and quantitative characteristics of the stimulus and the properties of the cell itself The effect of the effect depends on both the qualitative and quantitative characteristics of the stimulus and the properties of the cell itself

LAWS OF IRRITATION This is a set of rules that describe the requirements that a stimulus must obey so that it can cause the process of excitation. These include: the polar law, the law of force, the law of time (duration of action), the law of steepness (time of increase in force)

69 Laws of irritation Law of force Law of force - for an PD to occur, the strength of the stimulus must be no less than the threshold value. Law of time Law of time - for an AP to occur, the duration of the stimulus must be no less than the threshold value Law of slope Law of slope - for an AP to occur, the stimulus slope must be no less than the threshold value

Dependence of force on time of action P – rheobase is the minimum current strength that causes excitation PV – useful time is the minimum time of action of an irritating impulse with a force of one rheobase required for excitation. Chr - chronascia - the minimum duration of action of an irritating impulse with a force of 2 rheobases necessary for the occurrence of PD.

Accommodation This is the ability of tissue to adapt to a long-acting stimulus. At the same time, its strength also increases slowly (small steepness). This is the ability of the tissue to adapt to a long-acting stimulus. At the same time, its strength also increases slowly (small slope) The critical level of depolarization shifts towards zero The critical level of depolarization shifts towards zero Sodium channels do not open simultaneously and the sodium current into the cell is compensated by the potassium current from the cell. PD does not occur, because there is no regenerative depolarization. Sodium channels do not open simultaneously and the flow of sodium into the cell is compensated by the flow of potassium from the cell. PD does not occur, because there is no regenerative depolarization Accommodation manifests itself in an increase in the threshold strength of the stimulus as the steepness of the stimulus decreases - the lower the steepness, the greater the threshold force. The basis of tissue accommodation is the process of inactivation of sodium channels. Therefore, the lower the steepness of the stimulus increase, the more sodium channels are inactivated; the level of critical depolarization shifts and the threshold strength of the stimulus increases. If the steepness of the stimulus increase is less than the threshold value, then AP does not occur and only a local response will be observed.

PHYSIOLOGICAL ELECTROTONE Changes in the excitability of the membrane during prolonged exposure to a direct current of subthreshold force. catelectroton - In this case, catelectroton develops under the cathode - an increase in excitability. anelectroton under the anode - anelectroton - decreased excitability.

Electroton. A – catelectroton. 1 – initial increase in excitability: V1 V. B – anelectroton, decrease in excitability: V1 > V. V. B – anelectroton, decreased excitability: V1 > V."> V. B – anelectroton, decreased excitability: V1 > V."> V. B – anelectroton, decreased excitability: V1 > V." title="(!LANG :Electroton. A – catelectroton. 1 – initial increase in excitability: V1 V. B – anelectroton, decrease in excitability: V1 > V."> title="Electroton. A – catelectroton. 1 – initial increase in excitability: V1 V. B – anelectroton, decrease in excitability: V1 > V."> !}

Cathodic depression according to Verigo If a direct current acts on the membrane for a long time, then the increased excitability under the cathode changes to a decrease in excitability. This phenomenon is based on the phenomenon of tissue accommodation, because D.C. can be represented as a current with an infinitesimal slope of rise.

The electrical impulse that travels through the heart and triggers each contraction cycle is called an action potential; it represents a wave of short-term depolarization, during which the intracellular potential in each cell in turn becomes positive for a short time and then returns to its original negative level. Changes in the normal cardiac action potential have a characteristic development over time, which for convenience is divided into the following phases: phase 0 - initial rapid depolarization of the membrane; phase 1 - rapid but incomplete repolarization; phase 2 - “plateau”, or prolonged depolarization, characteristic of the action potential of cardiac cells; phase 3 - final fast repolarization; phase 4 - diastole period.
During an action potential, the intracellular potential becomes positive, since the excited membrane temporarily becomes more permeable to Na+ (compared to K+) , therefore, the membrane potential for some time approaches in value the equilibrium potential of sodium ions (ENa) - ENa can be determined using the Nernst ratio; at extracellular and intracellular Na+ concentrations of 150 and 10 mM, respectively, it will be:

However, the increased permeability to Na+ persists only for a short time, so that the membrane potential does not reach ENa and returns to the resting level after the end of the action potential.
The above changes in permeability, causing the development of the depolarization phase of the action potential, arise due to the opening and closing of special membrane channels, or pores, through which sodium ions easily pass. The gating is believed to regulate the opening and closing of individual channels, which can exist in at least three conformations - open, closed and inactivated. One gate corresponding to the activation variable " m" in the Hodgkin-Huxley description of sodium ion currents in the membrane of the squid giant axon, rapidly move to open a channel when the membrane is suddenly depolarized by a stimulus. Other gates corresponding to the inactivation variable " h"in the Hodgkin-Huxley description, during depolarization they move more slowly, and their function is to close the channel (Fig. 3.3). Both the steady-state distribution of gates within the channel system and the rate of their transition from one position to another depend on the level of membrane potential. Therefore, the terms “time-dependent” and “voltage-dependent” are used to describe membrane Na+ conductance.
If the resting membrane is suddenly depolarized to a positive potential (for example, in a voltage-clamp experiment), the activation gate will quickly change its position to open the sodium channels, and then the inactivation gate will slowly close them (Figure 3.3). The word "slow" here means that inactivation takes a few milliseconds, while activation occurs in a fraction of a millisecond. The gates remain in these positions until the membrane potential changes again, and for all gates to return to their original resting state, the membrane must be completely repolarized to a high negative potential level. If the membrane is repolarized only to a low level of negative potential, then some inactivation gates will remain closed and the maximum number of available sodium channels that can open upon subsequent depolarization will be reduced. (The electrical activity of cardiac cells in which sodium channels are completely inactivated will be discussed below.) Complete repolarization of the membrane at the end of a normal action potential ensures that all gates return to their original state and are therefore ready for the next action potential.

Rice. 3.3. Schematic representation of membrane channels for inward ion flows at the resting potential, as well as during activation and inactivation.
On the left is the sequence of channel states at a normal resting potential of -90 mV. At rest, the inactivation gates of both the Na+ channel (h) and the slow Ca2+/Na+ channel (f) are open. During activation upon excitation of the cell, the t-gate of the Na+ channel opens and the incoming flow of Na+ ions depolarizes the cell, which leads to an increase in the action potential (graph below). The h-gate then closes, thus inactivating Na+ conduction. As the action potential rises, the membrane potential exceeds the more positive threshold of the slow channel potential; their activation gate (d) opens and Ca2+ and Na+ ions enter the cell, causing the development of the plateau phase of the action potential. Gate f, which inactivates Ca2+/Na+ channels, closes much more slowly than gate h, which inactivates Na channels. The central fragment shows the behavior of the channel when the resting potential decreases to less than -60 mV. Most Na channel inactivation gates remain closed as long as the membrane is depolarized; The incoming flow of Na+ that occurs when the cell is stimulated is too small to cause the development of an action potential. However, the inactivation gate (f) of the slow channels does not close and, as shown in the fragment on the right, if the cell is sufficiently excited to open the slow channels and allow slowly incoming ion flows to pass, a slow development of an action potential is possible in response.

Rice. 3.4.
On the left is the action potential occurring at the resting potential level of -90 mV; this occurs when the cell is excited by an incoming impulse or some subthreshold stimulus that quickly lowers the membrane potential to values below the threshold level of -65 mV. On the right are the effects of two subthreshold and threshold stimuli. Subthreshold stimuli (a and b) do not reduce the membrane potential to the threshold level; therefore, no action potential occurs. The threshold stimulus (c) reduces the membrane potential exactly to the threshold level, at which an action potential then occurs.

The long refractory period after excitation of cardiac cells is due to the long duration of the action potential and the voltage dependence of the sodium channel gating mechanism. The rise phase of the action potential is followed by a period of hundreds to several hundred milliseconds during which there is no regenerative response to a repeated stimulus (Fig. 3.5). This is the so-called absolute, or effective, refractory period; it usually spans the plateau (phase 2) of the action potential. As described above, sodium channels are inactivated and remain closed during this sustained depolarization. During the repolarization of the action potential (phase 3), inactivation is gradually eliminated, so that the proportion of channels capable of reactivation constantly increases. Therefore, only a small influx of sodium ions can be elicited by the stimulus at the onset of repolarization, but such influxes will increase as the action potential repolarization continues. If some of the sodium channels remain non-excitable, the evoked influx of Na+ can lead to regenerative depolarization and hence an action potential. However, the rate of depolarization, and therefore the speed of propagation of action potentials, is significantly reduced (see Fig. 3.5) and normalizes only after complete repolarization. The time during which a repeated stimulus is able to produce such “gradual” action potentials is called the relative refractory period. The voltage dependence of the elimination of inactivation was studied by Weidmann, who found that the rate of rise of the action potential and the possible level at which this potential is evoked are in an S-shaped relationship, also known as the membrane reactivity curve.
The low rate of rise of action potentials evoked during the relative refractory period causes their slow propagation; Such action potentials can cause several conduction disturbances, such as delay, attenuation and blocking, and can even cause excitation circulation. These phenomena are discussed later in this chapter.
In normal cardiac cells, the incoming sodium current responsible for the rapid rise of the action potential is followed by a second incoming current, smaller and slower than the sodium current, which appears to be carried primarily by calcium ions. This current is usually referred to as the "slow inward current" (although it is only such in comparison to the fast sodium current; other important changes, such as those observed during repolarization, are probably slower); it flows through channels which, due to their time- and voltage-dependent conductivity characteristics, have been called “slow channels” (see Fig. 3.3). The activation threshold for this conductance (i.e., when the activation gate d begins to open) lies between -30 and -40 mV (compare: -60 to -70 mV for sodium conductance). The regenerative depolarization caused by the fast sodium current usually activates the conduction of the slow incoming current, so that during the later rise of the action potential, current flows through both types of channels. However, the Ca2+ current is much smaller than the maximum fast Na+ current, so its contribution to the action potential is very small until the fast Na+ current becomes sufficiently inactivated (i.e., after the initial rapid rise of the potential). Since the slow incoming current can only be inactivated very slowly, it contributes mainly to the plateau phase of the action potential. Thus, the plateau level shifts towards depolarization when the electrochemical potential gradient for Ca2+ increases with increasing concentration of [Ca2+]0; a decrease in [Ca2+]0 causes a shift in the plateau level in the opposite direction. However, in some cases there may be a contribution of calcium current to the rise phase of the action potential. For example, the action potential rise curve in frog ventricular myocardial fibers sometimes exhibits a bend around 0 mV, at the point where the initial fast depolarization gives way to a slower depolarization that continues until the peak of the action potential overshoot. It has been shown that the rate of slower depolarization and the magnitude of overshoot increase with increasing [Ca2+]0.
In addition to their different dependence on membrane potential and time, these two types of conductivity also differ in their pharmacological characteristics. Thus, the current through fast Na+ channels is reduced by tetrodotoxin (TTX), while the slow Ca2+ current is not affected by TTX, but is enhanced by catecholamines and inhibited by manganese ions, as well as some drugs such as verapamil and D-600. It seems very likely (at least in the frog heart) that most of the calcium needed to activate the proteins that contribute to each heartbeat enters the cell during the action potential through the slow inward current channel. In mammals, an available additional source of Ca2+ for cardiac cells is its reserves in the sarcoplasmic reticulum.

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