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Electrical heterogeneity of the heart. Myocardial contractility. Physiology. Critical level of depolarization Regenerative depolarization

The electrical impulse that propagates through the heart and starts each cycle of contractions is called an action potential; it is a wave of short-term depolarization, during which the intracellular potential alternately in each cell 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 rapid repolarization; phase 4 - period of diastole.

At 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 magnitude 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 after the end of the action potential returns to the resting level.

The above changes in permeability, which cause 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. It is believed that the work of the "gate" regulates 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 description of Hodgkin - Huxley, sodium ion fluxes in the membrane of the giant squid axon move rapidly, opening the channel when the membrane suddenly depolarizes under the influence of a stimulus. Other gates corresponding to the inactivation variable " h” in the Hodgkin-Huxley description, they move slower during depolarization, and their function is to close the channel (Fig. 3.3). Both the steady distribution of gates within a system of channels and the rate of their transition from one position to another depend on the level membrane potential. Therefore, the terms "time-dependent" and "potential-dependent" are used to describe Na+ membrane conductivity.

If the membrane at rest is suddenly depolarized to a positive potential level (for example, in a potential clamping experiment), the activation gate will quickly change position to open the sodium channels, and then the inactivation gate will slowly close them (Fig. 3.3). The word "slow" here means that the inactivation takes a few milliseconds, while the activation occurs in a fraction of a millisecond. The gates remain in these positions until the membrane potential changes again, and in order 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 repolarizes only to a low level of negative potential, then some of the 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, therefore, are ready for the next action potential.

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

On the left, the channel state sequence is shown 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; at the same time, their activation gates (d) open and Ca 2+ and Na + ions enter the cell, causing the development of the action potential plateau phase. 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 drops to less than -60 mV. Most Na-channel inactivation gates remain closed as long as the membrane is depolarized; the incoming flow of Na + arising from stimulation of the cell 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 let the slowly incoming ion flows through, a response slow development of the action potential is possible.

Rice. 3.4. Threshold potential during excitation of the heart cell.

On the left, an action potential occurring at a 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, the effects of two subthreshold and threshold stimuli. Subthreshold stimuli (a and b) do not lead to a decrease in the membrane potential to the threshold level; therefore, no action potential occurs. The threshold stimulus (c) lowers the membrane potential exactly to the threshold level, at which the action potential then arises.

Rapid depolarization at the beginning of the action potential is caused by a powerful influx of sodium ions entering the cell (corresponding to the gradient of their electrochemical potential) through open sodium channels. However, first of all, sodium channels must be effectively opened, which requires rapid depolarization of a sufficiently large membrane area to the required level, called the threshold potential (Fig. 3.4). In the experiment, this can be achieved by passing a current from an external source through the membrane and using an extracellular or intracellular stimulating electrode. Under natural conditions, local currents flowing through the membrane just before the propagating action potential serve the same purpose. 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, the depolarization causes more channels to open, resulting in an increase in the incoming ion flux, 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 entire depolarization phase from -90 mV to +30 mV, then the change potential at 120 mV would take about 0.25 ms. The maximum rate of depolarization of the fibers of the working myocardium of the ventricles is approximately 200 V / s, and that of the muscle fibers of the atria 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 referred to as "rapid responses") travel rapidly through the heart. The rate of action potential propagation (as well as Vmax) in cells with the same membrane carrying capacity and axial resistance characteristics is determined mainly by the amplitude of the inward current flowing during the rising phase of the action potential. This is due to the fact that the local currents passing through the cells immediately before the action potential have a larger value with a faster increase in potential, so the membrane potential in these cells reaches the threshold level earlier than in the case of currents of a smaller value (see Fig. 3.4) . Of course, these local currents flow through cell membrane and immediately after the passage of the propagating action potential, but they are no longer able to excite the membrane due to its refractoriness.

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

The amplitude and increase in speed of the 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 incapable of spreading (gradual or local responses). The "c" response is the earliest of the propagating action potentials, but its propagation is slow due to the slight increase in velocity as well as the low amplitude. The “d” response appears just before complete repolarization, its rate of increase and amplitude are higher than for the “c” response, since it occurs at a higher membrane potential; however, its propagation speed becomes lower than normal. The answer "d" is noted after complete repolarization, so its amplitude and depolarization rate are normal; hence, it spreads rapidly. PP - resting potential.

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 gate mechanism. The action potential rise phase is followed by a period of hundreds to several hundred milliseconds during which there is no regenerative response to the repeated stimulus (Fig. 3.5). This is the so-called absolute, or effective, refractory period; it usually covers a 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), the inactivation is gradually eliminated, so that the proportion of channels that can be activated again constantly increases. Therefore, only a small influx of sodium ions can be induced with a stimulus at the start of repolarization, but as the repolarization of the action potential continues, such fluxes will increase. If some of the sodium channels remain non-excitable, then the induced inward Na + flow can lead to regenerative depolarization and hence the generation of an action potential. However, the rate of depolarization, and hence the rate of propagation of action potentials, is significantly reduced (see Fig. 3.5) and normalize only after complete repolarization. The time during which a repeated stimulus is able to elicit 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 them to spread slowly; such action potentials can cause some conduction disturbances, such as delay, decay, and blocking, and may even cause excitation to circulate. These phenomena are discussed later in this chapter.

In normal cardiac cells, the inward sodium current responsible for the rapid rise of the action potential is followed by a second inward 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 so in comparison to the fast sodium current; other important changes, such as those seen during repolarization, are likely to be slowed down); it flows through channels which, according to their time- and voltage-dependent conductivity characteristics, have been called "slow channels" (see Figure 3.3). The activation threshold for this conductance (i.e. when the activation gate starts to open - d) lies between -30 and -40 mV (compare -60 to -70 mV for sodium conduction). The regenerative depolarization due to the fast sodium current usually activates the conduction of the slow incoming current, so that in the later period of the action potential rise, the current flows through both types of channels. However, the current Ca 2+ is much less 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 increase in 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 level of the plateau shifts towards depolarization, when the gradient of the electrochemical potential 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, the contribution of calcium current to the phase of the rise of the action potential may be noted. For example, the rise curve of the action potential in the myocardial fibers of the frog ventricle sometimes shows a kink around 0 mV, at the point where the initial rapid depolarization gives way to a slower depolarization that continues until the peak of the action potential overshoot. As has been shown, the rate of slower depolarization and the magnitude of the overshoot increase with increasing [Ca 2+ ] 0 .

In addition to different dependence on membrane potential and time, these two types of conductivity also differ in their pharmacological characteristics. So, the current through fast channels for Na + decreases under the influence of tetrodotoxin (TTX), while the slow current Ca 2+ is not affected by TTX, but increases under the action of catecholamines and is inhibited by manganese ions, as well as by some drugs, such as verapamil and D- 600 . It seems highly likely (at least in the frog's 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 channel for the incoming current. In mammals, an available additional source of Ca 2+ for cardiac cells is its reserves in the sarcoplasmic reticulum.

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

However, in any case, when there is a separation of charges, an electric potential immediately arises. Potential is a measure of the force that tends to bring together separated charges and eliminate polarization. The electric potential is therefore also called the electromotive force, which is abbreviated EMF.

Electric potential is called potential precisely because it does not actually set charges in motion, since there is an opposing force that keeps opposite electric charges from approaching. This force will exist as long as energy is spent to maintain it (which is what happens in cells). Thus, the force that seeks to bring charges closer together has only the ability, or potency, to do so, and such a convergence occurs only when the energy expended on the separation of charges weakens. Electric potential is measured in units called volts, after Volt, 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 equal to 70 millivolts, since a millivolt is equal to one thousandth of a volt. Of course, this is a very small potential compared to 120 volts (120,000 millivolts) of mains voltage. alternating current or compared to thousands of volts of voltage in power lines. But it's still amazing potential, given the materials the cell has at its disposal for building 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 equalize the charges. Thus, the membrane will become depolarized. Of course, this happens when the cell is damaged or killed. 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 leads to an expansion and (for reasons not yet known) will cause depolarization in this place. Heat causes the membrane to expand, cold shrinks it, and these mechanical changes also cause depolarization.

The effect on the membrane of some chemical compounds and the impact on it of weak electric currents leads to the same result.

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

The depolarization that occurred in one place of the membrane serves as a stimulus for the propagation of depolarization across the membrane. The sodium ion, which rushed into the cell at the place where the depolarization occurred and the sodium pump stopped, displaces the potassium ion. Sodium ions are smaller and 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 is again polarized, but with the opposite sign. At some point, the flare acquires an internal positive charge due to the presence of an excess of sodium ions in it. A small negative charge appears on the outside of the membrane.

Oppositely directed 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 rolls over the entire membrane. In the initial section, the polarization with the opposite sign cannot continue for a long time. Potassium ions continue to leave the cell, gradually their flow equalizes with the flow of incoming sodium ions. The positive charge inside the cell disappears. This disappearance of the reverse potential to some extent reactivates the sodium pump at that point 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 phase of repolarization. Since these events occur in all areas of membrane depolarization, a repolarization wave sweeps across the membrane following the depolarization wave.

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 wave of depolarization that has passed through a certain section of the membrane makes this section 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 response of the membrane to the stimulus is isolated and single. If the 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 be reduced; the entire muscle fiber will be reduced. 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 enough to give the impression that the muscle is contracting as a 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 electric current. This is not a waste of energy. If the stimulus is an attack by an enemy, then the electrical discharge can injure or kill him.

There are seven types of fish (some of them are bony, some are cartilaginous, 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 a very symbolic name - Electrophorus electricus. Electric eel - dweller fresh water, 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, it was so named for the long tail, which is four-fifths of the body of this animal, which is from 6 to 9 feet long. All the usual organs of this fish fit in the front of the body, about 15 to 16 inches long.

More than half of the long tail is occupied by a sequence of blocks of modified muscles that form an "electric organ". Each of these muscles produces a potential that does not exceed the potential of a normal muscle. But thousands and thousands of elements of this "battery" are connected in such a way that their potentials add up. Rested electric eel capable of accumulating a potential of the order of 600 - 700 volts and discharging it at a rate of 300 times per second. With fatigue, this figure drops to 50 times per second, but the eel can withstand this rate for a long time. The electric shock is strong enough to kill the small animal on which this fish feeds, or to inflict a sensitive defeat on a larger animal that mistakenly decides to eat an electric eel.

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 fangs and claws if they took up half the mass of their body.

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

In those cases where there is a separation of charges and positive charges are located in one place, and negative in another, physicists speak of charge polarization. Physicists use the term by analogy with the opposite magnetic forces that accumulate at opposite ends, or poles (the name is given because a freely moving magnetized strip points with its ends towards the geographic poles) of a bar magnet. In the case under discussion, we have a concentration of positive charges on one side of the membrane and a concentration of negative charges on the other side of the membrane, that is, we can speak of a polarized membrane.

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 equal to 70 millivolts, since a millivolt is equal to one thousandth of a volt. Of course, this is a very small potential compared to 120 volts (120,000 millivolts) of voltage in the AC mains or compared to thousands of volts of voltage in power lines. But it's still amazing potential, given the materials the cell has at its disposal for building electrical systems.

The effect on the membrane of some chemical compounds and the impact on it of weak electric currents leads to the same result. (In the latter case, the cause of the depolarization seems to be the most obvious. After all, why can't the electrical phenomenon of polarization be changed by an externally applied electrical potential?)

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

More than half of the long tail is occupied by a sequence of blocks of modified muscles that form an "electric organ". Each of these muscles produces a potential that does not exceed the potential 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 able to accumulate a potential of the order of 600 - 700 volts and discharge it at a rate of 300 times per second. When fatigued, this figure drops to 50 times per second, but the eel can withstand this rate for a long time. The electric shock is strong enough to kill the small animal on which this fish feeds, or to inflict a sensitive defeat on a larger animal that mistakenly decides to eat an electric eel.

NEURON

The seals that we can observe with the naked eye are certainly not individual cells. These are bundles of nerve fibers, sometimes these bundles contain a lot of fibers, each of which is part of a nerve cell. All the fibers in the bundle run in the same direction and, for the sake of convenience and space, are interconnected, although individual fibers may perform completely different functions. In the same way, separate insulated electrical wires performing completely different tasks are combined into one electrical cable for convenience. The nerve fiber itself is part of a nerve cell, also called a neuron. It is a Greek derivative of the Latin word for nerve. The Greeks of the Hippocratic era applied the word to nerves in the true sense and to tendons. Now this term refers exclusively to the individual nerve cell. The main part of the neuron - the body is practically not much different from all other cells of the body. The body contains a nucleus and cytoplasm. The biggest difference between a nerve cell and other cells is the presence of long outgrowths from the cell body. Outgrowths branch out from most of the surface of the body of the nerve cell, which branch along the length. These branching outgrowths resemble the crown of a tree and are called dendrites (from the Greek word for "tree").

There is one place on the surface of the cell body, from which one, especially long, process emerges, which does not branch along its entire (sometimes huge) length. This process is called an axon. Why it is so called, I will explain later. It is the axons that represent the typical nerve fibers of the nerve bundle. Although the axon is microscopically thin, it can be several feet long, which seems unusual when you consider that the axon is just part of a single nerve cell.

The depolarization that has arisen in any part of the nerve cell propagates at high speed along the fiber. The wave of depolarization propagating along the processes of a nerve cell is called a nerve impulse. The pulse can propagate along the fiber in any direction; so, if you apply a stimulus to the middle of the fiber, then the impulse will propagate in both directions. However, in living systems, it almost always turns out that the impulses propagate along the dendrites in only one direction - towards the cell body. Along the axon, the impulse always propagates from the cell body.

The speed of propagation of an impulse along a nerve fiber was first measured in 1852 by the German scientist Hermann Helmholtz. To do this, he applied stimuli to the nerve fiber at different distances from the muscle and recorded the time after which the muscle contracted. If the distance increased, then the delay lengthened, after which the contraction occurred. The delay corresponded to the time it took for the impulse to travel the additional distance.

Quite interesting is the fact that six years before Helmholtz's experiment, the famous German physiologist Johannes Müller, in a fit of conservatism, so characteristic of scientists at the slope of their careers, categorically stated that no one would ever be able to measure the speed of impulse conduction along the nerve.

In different fibers, the speed of impulse conduction is not the same. First, the speed at which an impulse travels along an axon depends roughly on its thickness.

The thicker the axon, the greater the speed of impulse propagation. In very thin fibers, the impulse travels along them quite slowly, at a speed of two meters per second or even less. No faster than, say, a wave of depolarization propagates through muscle fibers. Obviously, the faster the organism should respond to this or that stimulus, the more desirable is the high speed of impulse conduction. One way to achieve this state is to increase the thickness of the nerve fibers. In the human body, the thinnest fibers are 0.5 microns in diameter (a micron is one thousandth of a millimeter), while the thickest fibers are 20 microns, that is, 40 times larger. The cross-sectional area of thick fibers is 1600 times that of thin fibers.

One might think that since mammals have a better developed nervous system than other groups of animals, their nerve impulses propagate at the highest speed, and the nerve fibers are thicker than all the rest. species. But in reality this is not so. In lower animals, cockroaches, the nerve fibers are thicker than in humans.

The thickest nerve fibers have the most developed of the mollusks - squid. Large squids in general are probably the most developed and highly organized animals of all invertebrates. Given their physical size, we are not surprised that they require high conduction rates and very thick axons. The nerve fibers that go to the muscles of the squid are called giant axons and reach a diameter of 1 millimeter. This is 50 times the diameter of the thickest mammalian axon, and the cross-sectional area of squid axons exceeds mammalian axons by 2500 times. Giant squid axons are a godsend for neurophysiologists, who can easily perform experiments on them (for example, measure potentials on axonal membranes), which is very difficult to do on extremely thin vertebrate axons.

Nevertheless, why did invertebrates still surpass vertebrates in the thickness of nerve fibers, although vertebrates have a more developed nervous system?

The answer is that nerve conduction speed in vertebrates depends on more than axonal thickness. Vertebrates have at their disposal a more sophisticated way to increase the speed of conduction of impulses along axons.

In vertebrates, nerve fibers in the early stages of development of the organism fall into the environment of the so-called satellite cells. Some of these cells are called Schwann cells (after the German zoologist Theodor Schwain, one of the founders of the cellular theory of life). Schwann cells wrap around the axon, forming a tighter and tighter spiral, wrapping the fiber in a fat-like sheath called the myelin sheath. Ultimately, the Schwann cells form a thin sheath around the axon called the neurilemma, which nevertheless contains the nuclei of the original Schwann cells. (By the way, Schwann himself described these neurilemmas, which are sometimes called the Schwannian membrane in his honor. It seems to me that the term that refers to a tumor emanating from a neurilemma sounds very unmusical and insulting to the memory of a great zoologist. It is called a schwannoma.)

One individual Schwann cell envelops only a limited section of the axon. As a result, the Schwann sheaths cover the axon in separate sections, between which there are narrow areas in which the myelin sheath is absent. As a result, under a microscope, the axon looks like a bunch of sausages. The unmyelinated areas of this ligament are called nodes of Ranvier, after the French histologist Louis Antoine Ranvier, who described them in 1878. Thus, the axon is like a thin rod threaded through a series of cylinders along their axes. Axis on the Latin means "axis", hence the name of this process of the nerve cell. Suffix -is he attached, apparently by analogy with the word "neuron".

The function of the myelin sheath is not entirely clear. The simplest assumption about its function is that it serves as a kind of nerve fiber insulator, reducing the leakage of current in environment. Such leakage increases as the fiber gets thinner, and the presence of the insulator allows the fiber to remain thin without increasing potential loss. The evidence for this is based on the fact that myelin is predominantly composed of lipid (fat-like) materials, which are indeed excellent electrical insulators. (It is this material that gives the nerve its white color. Those about the nerve cell are colored gray.)

However, if myelin only served as an electrical insulator, then simpler fat molecules could do the job. But as it turned out, the chemical composition of myelin is very complex. Of every five myelin molecules, two are cholesterol molecules, two more are phospholipid molecules (fat molecules containing phosphorus), and the fifth molecule is cerebroside (a complex fat-like molecule containing sugar). There are other unusual substances in myelin. It seems highly probable that myelin performs in the nervous system by no means only the functions of an electrical insulator.

It has been suggested that the cells of the myelin sheath maintain the integrity of the axon because it is extended so far from the body of the nerve cell that it is likely to lose its normal connection with the nucleus of its nerve cell. It is known that the nucleus is vital for maintaining the normal functioning of any cell and all its parts. Perhaps the nuclei of Schwann cells take on the function of nannies that feed the axon in the areas that they envelop. After all, the axons of nerves, even devoid of myelin, are covered with a thin layer of Schwann cells, in which, of course, there are nuclei.

Finally, the myelin sheath somehow speeds up the conduction of the impulse along the nerve fiber. A fiber covered with a myelin sheath conducts impulses much faster than a fiber of the same diameter but without a myelin sheath. This is why vertebrates have won the evolutionary battle against invertebrates. They retained thin nerve fibers, but significantly increased the speed of impulse conduction through them.

Mammalian myelinated nerve fibers conduct nerve impulses at about 100 m/s, or, if you prefer, 225 miles per hour. That's pretty decent speed. The largest distance a mammalian nerve impulse has to travel is the 25 meters that separate a blue whale's head from its tail. nerve impulse passes this long way in 0.3 s. The distance from the head to the big toe in a person is an impulse along the myelinated fiber in one fiftieth of a second. With regard to the speed of information transfer in the nervous and endocrine systems, there is a huge and quite obvious difference.

When a baby is born, the process of melinating the nerves in his body is not yet complete, and various functions do not develop properly until the right nerves are myelinated. So, the child does not see anything at first. The function of vision is established only after myelination of the optic nerve, which, fortunately, does not take long. Similarly, the nerves to the muscles of the arms and legs remain unmyelinated during the first year of life, so the motor coordination necessary for independent movement is established only by this time.

Sometimes adults suffer from the so-called "demyelinating disease", in which there is a degeneration of myelin sections with subsequent loss of function of the corresponding nerve fiber. The best studied of these diseases is known as multiple sclerosis. This name is given to this disease because with it in various areas nervous system foci of myelin degeneration appear with its replacement with denser scar tissue. Such demyelination may develop as a result of the action on myelin of some protein present in the patient's blood. This protein appears to be an antibody, a member of a class of substances that normally only interact with foreign proteins but often cause symptoms of the condition we know as allergy. In fact, the multiple sclerosis patient develops an allergy to himself, and this disease may be an example of an autoallergic disease. Because sensory nerves are most commonly affected, the most common symptoms of multiple sclerosis are double vision, loss of tactile sensation, and other sensory disturbances. Multiple sclerosis most often affects people between the ages of 20 and 40. The disease can progress, that is, more and more nerve fibers can be affected, and eventually death occurs. However, the progression of the disease can be slow, and many patients live more than ten years from the time of diagnosis.

All nervous activity successfully functions due to the alternation of phases of rest and excitability. Failures in the polarization system disrupt the electrical conductivity of the fibers. But besides nerve fibers, there are other excitable tissues - endocrine and muscle.

But we will consider the features of conductive tissues, and using the example of the excitation process organic cells Let's talk about the significance of the critical level of depolarization. The physiology of nervous activity is closely related to the indicators of electric charge inside and outside the nerve cell.

If one electrode is attached to the outer shell of the axon, and the other to its inner part, then a potential difference is visible. The electrical activity of the nerve pathways is based on this difference.

What is resting potential and action potential?

All cells of the nervous system are polarized, that is, they have a different electrical charge inside and outside a special membrane. A nerve cell always has its own lipoprotein membrane, which has the function of a bioelectric insulator. Thanks to the membranes, a resting potential is created in the cell, which is necessary for subsequent activation.

The resting potential is maintained by the transfer of ions. The release of potassium ions and the entry of chlorine increase the membrane resting potential.

The action potential accumulates in the phase of depolarization, that is, the rise of an electric charge.

Action potential phases. Physiology

So, depolarization in physiology is a decrease in membrane potential. Depolarization is the basis for the emergence of excitability, that is, the action potential for a nerve cell. When a critical level of depolarization is reached, no, even a strong stimulus, is able to cause reactions in nerve cells. At the same time, there is a lot of sodium inside the axon.

Immediately after this stage, the phase of relative excitability follows. The answer is already possible, but only to a strong stimulus signal. Relative excitability slowly passes into the phase of exaltation. What is exaltation? This is the peak of tissue excitability.

All this time the sodium activation channels are closed. And their opening will occur only when it is discharged. Repolarization is needed to restore the negative charge inside the fiber.

What does the critical level of depolarization (CDL) mean?

So, excitability, in physiology, is the ability of a cell or tissue to respond to a stimulus and generate some kind of impulse. As we found out, cells need a certain charge - polarization - to work. The increase in charge from minus to plus is called depolarization.

Depolarization is always followed by repolarization. The charge inside after the excitation phase must become negative again so that the cell can prepare for the next reaction.

When the voltmeter readings are fixed at around 80 - rest. It occurs after the end of repolarization, and if the device shows a positive value (greater than 0), then the reverse repolarization phase is approaching the maximum level - the critical level of depolarization.

How are impulses transmitted from nerve cells to muscles?

The electrical impulses that have arisen during the excitation of the membrane are transmitted along the nerve fibers at high speed. The speed of the signal is explained by the structure of the axon. The axon is partially enveloped by a sheath. And between the areas with myelin are intercepts of Ranvier.

Thanks to this arrangement of the nerve fiber, a positive charge alternates with a negative one, and the depolarization current propagates almost simultaneously along the entire length of the axon. The contraction signal reaches the muscle in a fraction of a second. Such an indicator as the critical level of membrane depolarization means the mark at which the peak action potential is reached. After muscle contraction, repolarization starts along the entire axon.

What happens during depolarization?

What does such an indicator as a critical level of depolarization mean? In physiology, this means that the nerve cells are already ready to work. The correct functioning of the whole organ depends on the normal, timely change of phases of the action potential.

The critical level (CLL) is approximately 40-50 Mv. At this time, the electric field around the membrane decreases. directly depends on how many sodium channels of the cell are open. The cell at this time is not yet ready for a response, but collects an electrical potential. This period is called absolute refractoriness. The phase lasts only 0.004 s in nerve cells, and in cardiomyocytes - 0.004 s.

After passing a critical level of depolarization, superexcitability sets in. Nerve cells can respond even to the action of a subthreshold stimulus, that is, a relatively weak effect of the environment.

Functions of sodium and potassium channels

So, an important participant in the processes of depolarization and repolarization is the protein ion channel. Let's figure out what this concept means. ion channels- these are protein macromolecules located inside the plasma membrane. When they are open, inorganic ions can pass through them. Protein channels have a filter. Only sodium passes through the sodium duct, and only this element passes through the potassium duct.

These electrically controlled channels have two gates: one is an activation gate that has the ability to pass ions, the other is an inactivation one. At a time when the resting membrane potential is -90 mV, the gate is closed, but when depolarization begins, sodium channels slowly open. An increase in potential leads to a sharp closure of the duct valves.

The factor that affects the activation of channels is the excitability of the cell membrane. Under the influence of electrical excitability, 2 types of ion receptors are launched:

the action of ligand receptors is launched - for chemodependent channels;
an electrical signal is supplied for electrically controlled channels.

When a critical level of cell membrane depolarization is reached, receptors give a signal that all sodium channels need to be closed, and potassium channels begin to open.

Sodium Potassium Pump

The processes of transferring the excitation impulse everywhere take place due to the electric polarization carried out due to the movement of sodium and potassium ions. The movement of elements occurs on the basis of the principle of ions - 3 Na + inside and 2 K + outside. This exchange mechanism is called the sodium-potassium pump.

Depolarization of cardiomyocytes. Phases of the contraction of the heart

Cardiac cycles of contractions are also associated with electrical depolarization of the conduction pathways. The contraction signal always comes from the SA cells located in the right atrium and propagates along the Hiss pathways to the Torel and Bachmann bundles to the left atrium. The right and left processes of the bundle of Hiss transmit the signal to the ventricles of the heart.

Nerve cells depolarize faster and carry the signal due to the presence, but muscle tissue also gradually depolarizes. That is, their charge changes from negative to positive. This phase of the cardiac cycle is called diastole. All cells here are interconnected and act as one complex, since the work of the heart must be coordinated as much as possible.

When a critical level of depolarization of the walls of the right and left ventricles occurs, an energy release is generated - the heart contracts. Then all cells repolarize and prepare for a new contraction.

Depression Verigo

In 1889, a phenomenon in physiology was described, which is called Verigo's catholic depression. The critical level of depolarization is the level of depolarization at which all sodium channels are already inactivated, and potassium channels work instead. If the degree of current increases even more, then the excitability of the nerve fiber is significantly reduced. And the critical level of depolarization under the action of stimuli goes off scale.

During Verigo's depression, the rate of excitation conduction decreases, and, finally, completely subsides. The cell begins to adapt by changing functional features.

Adaptation mechanism

It happens that under certain conditions the depolarizing current does not switch for a long time. This is characteristic of sensory fibers. A gradual long-term increase in such a current in excess of 50 mV leads to an increase in the frequency of electronic pulses.

In response to such signals, the conductivity of the potassium membrane increases. Slower channels are activated. As a result, the ability of the nervous tissue to repeat responses arises. This is called nerve adaptation.

During adaptation, instead of a large number of short signals, cells begin to accumulate and give off a single strong potential. And the intervals between two reactions increase.

The electrical impulse that propagates through the heart and starts each cycle of contractions is called an action potential; it is a wave of short-term depolarization, during which the intracellular potential alternately in each cell 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 rapid repolarization; phase 4 - period of diastole.

At 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 magnitude the equilibrium potential of sodium ions (E Na) - E N and 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 after the end of the action potential returns to the resting level.

The above changes in permeability, which cause 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. It is believed that the operation of the gate regulates the opening and closing of individual channels, which can exist in at least three conformations - open, closed and inactivated. One gate corresponding to an activation variable m in the Hodgkin-Huxley description of the sodium ion currents in the membrane of the giant squid axon, move rapidly to open the channel when the membrane is suddenly depolarized by a stimulus. Other gates corresponding to the inactivation variable h in the description of Hodgkin - Huxley, they move slower during depolarization, and their function is to close the channel (Fig. 3.3). Both the steady distribution of gates within the channel system and the rate of their transition from one position to another depend on the level of the membrane potential. Therefore, the terms time-dependent and voltage-dependent are used to describe Na+ membrane conductivity.

If the membrane at rest is suddenly depolarized to a positive potential level (for example, in a potential clamping experiment), the activation gate will quickly change position to open the sodium channels, and then the inactivation gate will slowly close them (Fig. 3.3). The word slow here means that inactivation takes a few milliseconds, while activation occurs in fractions of a millisecond. The gates remain in these positions until the membrane potential changes again, and in order 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 repolarizes only to a low level of negative potential, then some of the 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, therefore, are ready for the next action potential.

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

On the left, the channel state sequence is shown 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; at the same time, their activation gates (d) open and Ca 2+ and Na + ions enter the cell, causing the development of the action potential plateau phase. 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 drops 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 during cell stimulation 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 let the slowly incoming ion flows through, a response slow development of the action potential is possible.

Rice. 3.4. Threshold potential during excitation of the heart cell.

The rapid depolarization at the beginning of the action potential is caused by a powerful influx of sodium ions entering the cell (corresponding to the gradient of their electrochemical potential) through open sodium channels. However, first of all, sodium channels must be effectively opened, which requires rapid depolarization of a sufficiently large membrane area to the required level, called the threshold potential (Fig. 3.4). In the experiment, this can be achieved by passing a current from an external source through the membrane and using an extracellular or intracellular stimulating electrode. Under natural conditions, local currents flowing through the membrane just before the propagating action potential serve the same purpose. 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, the depolarization causes more channels to open, resulting in an increase in the incoming ion flux, 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 entire depolarization phase from -90 mV to +30 mV, then the change potential at 120 mV would take about 0.25 ms. The maximum rate of depolarization of the fibers of the working myocardium of the ventricles is approximately 200 V / s, and that of the muscle fibers of the atria, 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 referred to as fast responses) travel quickly through the heart. The rate of action potential propagation (as well as Vmax) in cells with the same membrane carrying capacity and axial resistance characteristics is determined mainly by the amplitude of the inward current flowing during the rising phase of the action potential. This is due to the fact that the local currents passing through the cells immediately before the action potential have a larger value with a faster increase in potential, so the membrane potential in these cells reaches the threshold level earlier than in the case of currents of a smaller value (see Fig. 3.4) . Of course, these local currents flow through the cell membrane immediately after the passage of the propagating action potential, but they are no longer able to excite the membrane due to its refractoriness.

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

The amplitude and increase in speed of the 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 incapable of spreading (gradual or local responses). The response in represents the earliest of the propagating action potentials, but its propagation is slow due to a slight increase in speed, as well as low amplitude. Response d appears just before complete repolarization, its rate of increase and amplitude are higher than for response c, since it occurs at a higher membrane potential; however, its propagation speed becomes lower than normal. Response d is noted after complete repolarization, so its amplitude and depolarization rate are normal; hence, it spreads rapidly. PP - resting potential.

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 gate mechanism. The action potential rise phase is followed by a period of hundreds to several hundred milliseconds during which there is no regenerative response to the repeated stimulus (Fig. 3.5). This is the so-called absolute, or effective, refractory period; it usually covers a 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), the inactivation is gradually eliminated, so that the proportion of channels that can be activated again constantly increases. Therefore, only a small influx of sodium ions can be induced with a stimulus at the start of repolarization, but as the repolarization of the action potential continues, such fluxes will increase. If some of the sodium channels remain non-excitable, then the induced inward Na + flow can lead to regenerative depolarization and hence the generation of an action potential. However, the rate of depolarization, and hence the rate of propagation of action potentials, is significantly reduced (see Fig. 3.5) and normalize only after complete repolarization. The time during which a repeated stimulus is able to elicit 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.

In normal cardiac cells, the inward sodium current responsible for the rapid rise of the action potential is followed by a second inward 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 so in comparison to the fast sodium current; other important changes, such as those seen during repolarization, are likely to slow down); it flows through the channels, which, in accordance with the characteristics of their conductivity, depending on time and voltage, have been called slow channels (see Fig. 3.3). The activation threshold for this conductance (i.e. when the activation gate starts to open - d) lies between -30 and -40 mV (compare -60 to -70 mV for sodium conduction). The regenerative depolarization due to the fast sodium current usually activates the conduction of the slow incoming current, so that in the later period of the action potential rise, the current flows through both types of channels. However, the current Ca 2+ is much less 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 increase in 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 level of the plateau shifts towards depolarization, when the gradient of the electrochemical potential for Ca 2+ increases with increasing concentration of 0 ; a decrease in 0 causes a shift in the plateau level in the opposite direction. However, in some cases, the contribution of calcium current to the phase of the rise of the action potential may be noted. For example, the rise curve of the action potential in the myocardial fibers of the frog ventricle sometimes shows a kink around 0 mV, at the point where the initial rapid depolarization gives way to a slower depolarization that continues until the peak of the action potential overshoot. As has been shown, the rate of slower depolarization and the amount of overshoot increase with increasing 0.

In addition to different dependence on membrane potential and time, these two types of conductivity also differ in their pharmacological characteristics. So, the current through fast channels for Na + decreases under the influence of tetrodotoxin (TTX), while the slow current Ca 2+ is not affected by TTX, but increases under the action of catecholamines and is inhibited by manganese ions, as well as by some drugs, such as verapamil and D - 600 . It seems highly likely (at least in the frog's 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 channel for the incoming current. In mammals, an available additional source of Ca 2+ for cardiac cells is its reserves in the sarcoplasmic reticulum.