Action potential is the mechanism of property formation. Action potential, its phases

The functioning of the organs and tissues of our body depends on many factors. Some cells (cardiomyocytes and nerves) depend on the transmission of nerve impulses generated in special cell components or nodes. It is based on the formation of a specific excitation wave called an action potential.

What it is?

An action potential is a wave of excitation that moves from cell to cell. Due to its formation and passage through, a short-term change in their charge occurs (normally, the inner side of the membrane is negatively charged, and the outer side is positively charged). The generated wave promotes a change in the properties of the cell’s ion channels, which leads to recharging of the membrane. At the moment when the action potential passes through the membrane, a short-term change in its charge occurs, which leads to a change in the properties of the cell.

The formation of this wave underlies the functioning of the cardiac conduction system.

When its formation is disrupted, many diseases develop, which makes the determination of the action potential necessary in a complex of diagnostic and treatment measures.

How is an action potential formed and what is characteristic of it?

History of the study

The study of the occurrence of excitation in cells and fibers began quite a long time ago. Its occurrence was first noticed by biologists who studied the effects of various stimuli on the exposed tibial nerve of a frog. They noticed that when exposed to a concentrated solution of table salt, muscle contraction was observed.

Subsequently, research was continued by neurologists, but the main science after physics that studies the action potential is physiology. It was physiologists who proved the presence of action potentials in heart cells and nerves.

As we delved deeper into the study of potentials, the presence of a resting potential was also proven.

Since the beginning of the 19th century, methods began to be created that made it possible to record the presence of these potentials and measure their magnitude. Currently, recording and studying action potentials is carried out in two instrumental studies - taking electrocardiograms and electroencephalograms.

Action potential mechanism

The formation of excitation occurs due to changes in the intracellular concentration of sodium and potassium ions. Normally, the cell contains more potassium than sodium. The extracellular concentration of sodium ions is significantly higher than in the cytoplasm. Changes caused by the action potential contribute to a change in the charge on the membrane, resulting in the flow of sodium ions into the cell. Because of this, the charges outside change and the inside becomes positively charged, while the external environment becomes negatively charged.

This is done to facilitate the passage of the wave through the cell.

After the wave has been transmitted through the synapse, the charge is restored due to the flow of negatively charged chlorine ions into the cell. The original charge levels outside and inside the cell are restored, which leads to the formation of a resting potential.

Periods of rest and excitement alternate. In a pathological cell, everything can happen differently, and the formation of PD there will obey slightly different laws.

PD phases

The course of an action potential can be divided into several phases.

The first phase occurs before formation (a passing action potential stimulates the slow discharge of the membrane, which reaches a maximum level, usually around -90 mEV). This phase is called pre-spike. It is carried out due to the entry of sodium ions into the cell.

The next phase, the peak potential (or spike), forms a parabola with an acute angle, where the ascending part of the potential means depolarization of the membrane (fast), and the descending part means repolarization.

The third phase - negative trace potential - shows trace depolarization (the transition from the peak of depolarization to the resting state). Caused by the entry of chlorine ions into the cell.

At the fourth stage, the positive trace potential phase, the membrane charge levels return to the original level.

These phases, caused by the action potential, strictly follow one after another.

Functions of action potential

Undoubtedly, the development of the action potential is important in the functioning of certain cells. In the work of the heart, excitation plays a major role. Without it, the heart would simply be an inactive organ, but due to the propagation of the wave through all the cells of the heart, it contracts, which helps push blood through the vascular bed, enriching all tissues and organs with it.

It also could not perform its function normally without an action potential. Organs could not receive signals to perform one or another function, as a result of which they would simply be useless. In addition, the improvement of the transmission of nerve impulses in nerve fibers (the appearance of myelin and nodes of Ranvier) made it possible to transmit a signal in a matter of seconds, which led to the development of reflexes and conscious movements.

In addition to these organ systems, the action potential is also formed in many other cells, but in them it plays a role only in the cell performing its specific functions.

The occurrence of an action potential in the heart

The main organ whose work is based on the principle of action potential formation is the heart. Due to the existence of impulse generation nodes, the work of this organ is carried out, the function of which is to deliver blood to tissues and organs.

The generation of action potentials in the heart occurs in the sinus node. It is located at the confluence of the vena cava in the right atrium. From there, the impulse spreads along the fibers of the conduction system of the heart - from the node to the atrioventricular connection. Passing more precisely, along its legs, the impulse passes to the right and left ventricles. In their thickness there are smaller conduction pathways - Purkinje fibers, through which excitation reaches each heart cell.

The action potential of cardiomyocytes is composite, i.e. depends on the contraction of all cells of the cardiac tissue. In the presence of a block (scar after a heart attack), the formation of an action potential is disrupted, which is recorded on the electrocardiogram.

Nervous system

How is AP formed in neurons - cells of the nervous system? Here everything is done a little easier.

An external impulse is perceived by the processes of nerve cells - dendrites, associated with receptors located both in the skin and in all other tissues (resting potential and action potential also replace each other). Irritation provokes the formation of an action potential in them, after which the impulse goes through the body of the nerve cell to its long process - the axon, and from it through synapses - to other cells. Thus, the generated wave of excitation reaches the brain.

A feature of the nervous system is the presence of two types of fibers - covered with myelin and without it. The emergence of an action potential and its transmission in those fibers where there is myelin occurs much faster than in demyelinated ones.

This phenomenon is observed due to the fact that the propagation of AP along myelinated fibers occurs due to “jumping” - the impulse jumps over sections of myelin, which as a result reduces its path and, accordingly, accelerates propagation.

Resting potential

Without the development of the resting potential there would be no action potential. The resting potential is understood as the normal, unexcited state of the cell, in which the charges inside and outside its membrane are significantly different (that is, the outside of the membrane is positively charged, and the inside is negative). The resting potential shows the difference between the charges inside and outside the cell. Normally it is between -50 and -110 mEv. In nerve fibers this value is usually -70 mEv.

It is caused by the migration of chloride ions into the cell and the creation of a negative charge on the inner side of the membrane.

When the concentration of intracellular ions changes (as mentioned above), the PP replaces the PD.

Normally, all cells of the body are in an unexcited state, so the change in potentials can be considered a physiologically necessary process, since without them the cardiovascular and nervous systems could not carry out their activities.

The importance of studying resting and action potentials

The resting potential and action potential make it possible to determine the state of the body, as well as individual organs.

Recording the action potential from the heart (electrocardiography) allows us to determine its condition, as well as the functional ability of all its parts. If you study a normal ECG, you will notice that all the waves on it are a manifestation of the action potential and the subsequent resting potential (accordingly, the occurrence of these potentials in the atria reflects the P wave, and the spread of excitation in the ventricles - the R wave).

As for the electroencephalogram, the appearance of various waves and rhythms (in particular, alpha and beta waves in a healthy person) is also due to the emergence of action potentials in the neurons of the brain.

These studies make it possible to timely identify the development of a particular pathological process and determine almost up to 50 percent of successful treatment of the original disease.

An action potential is a rapid change in membrane potential that occurs when nerve, muscle, and some glandular cells are excited. Its occurrence is based on changes in the ionic permeability of the membrane. There are four consecutive periods in the development of an action potential: 1) local response; 2) depolarization; 3) repolarization and 4) trace potentials (Fig. 2.11).

Local response is an active local depolarization resulting from an increase in sodium permeability of the cell membrane. A decrease in membrane potential is called depolarization. However, with a subthreshold stimulus, the initial increase in sodium permeability is not large enough to cause rapid membrane depolarization. A local response occurs not only at subthreshold, but also at suprathreshold

Rice. 2.11.

1 - local response; 2 - depolarization phase; 3 - repolarization phase; 4 - negative trace potential; 5 - positive (hyperpolarization) trace potential

stimulation and is a component of the action potential. Thus, the local response is the initial and universal form of tissue response to stimulation of varying strengths. The biological meaning of the local response is that if the stimulus is small in strength, then the tissue reacts to it with minimal energy expenditure, without turning on the mechanisms of specific activity. In the same case, when the stimulation is suprathreshold, the local response turns into an action potential. The period from the beginning of stimulation to the beginning of the depolarization phase, when the local response, increasing, reduces the membrane potential to a critical level (CLP), is called the latent or latent period, the duration of which depends on the strength of stimulation (Fig. 2.12).

Depolarization phase characterized by a rapid decrease in membrane potential and even recharging of the membrane: its inner part becomes positively charged for some time, and the outer part becomes negatively charged. The change in the sign of charge on the membrane is called perversion - reversion of potential. Unlike the local response, the speed and magnitude of depolarization do not depend on the strength of the stimulus. The duration of the depolarization phase in a frog nerve fiber is about 0.2-0.5 ms.

Duration repolarization phases is 0.5-0.8 ms. Restoring the original value of membrane polarization is called repolarization. During this time, the membrane potential

Rice. 2.12. Action potentials arising in response to threshold stimulation with short (A) and long-term (B) stimuli. Irritating stimuli, under the influence of which responses A and B are obtained: PP - resting potential; Ekud. - critical level of membrane depolarization (according to A.L. Katalymov)

cial is gradually restored and reaches 75-85% of the resting potential. In the literature, the second and third periods are often called peak of the action potential.

The fluctuations in membrane potential following the peak of the action potential are called trace potentials. There are two types of trace potentials - trace depolarization and trace hyperpolarization, which correspond to the fourth and fifth phases of the action potential. Trace depolarization (negative trace potential) is a continuation of the repolarization phase and is characterized by a slower (compared to the repolarization phase) restoration of the resting potential. The trace depolarization turns into a trace hyperpolarization (positive trace potential), which is a temporary increase in the membrane potential above the initial level. An increase in membrane potential is called hyperpolarization. In myelinated nerve fibers, trace potentials are more complex: trace depolarization can turn into trace hyperpolarization, then sometimes a new depolarization occurs, only after which the resting potential is completely restored.

Ionic mechanism of action potential occurrence. The basis of the action potential is the changes in the ionic permeability of the cell membrane that develop sequentially over time.

When a cell is exposed to an irritant, the permeability of the membrane for Na + ions sharply increases due to the activation (opening) of sodium channels.

In this case, Na + ions intensively move along the concentration gradient from outside to intracellular space. The entry of Na + ions into the cell is also facilitated by electrostatic interaction. As a result, the permeability of the membrane for Na + becomes 20 times greater than the permeability for K + ions.

At first, depolarization occurs relatively slowly. When the membrane potential decreases by 10-40 mV, the rate of depolarization increases sharply and the action potential curve rises steeply. The level of membrane potential at which the rate of membrane depolarization sharply increases due to the fact that the flow of Na + ions into the cell is greater than the flow of K + ions out is called critical level of depolarization.

As the flow of Na + into the cell begins to exceed the potassium current from the cell, a gradual decrease in the resting potential occurs, leading to a reversion - a change in the sign of the membrane potential. In this case, the inner surface of the membrane becomes electropositive with respect to its outer electronegative surface. These changes in membrane potential correspond to the ascending phase of the action potential (depolarization phase).

The membrane is characterized by increased permeability to Na + ions only for a very short time (0.2-0.5 ms). After this, the permeability of the membrane for Na + ions decreases again, and for K + it increases. As a result, the flow of Na + into the cell is sharply weakened, and the flow of K + from the cell increases.

During an action potential, a significant amount of Na + enters the cell, and K + ions leave the cell. Restoration of the cellular ionic balance is carried out thanks to the work of the sodium-potassium pump, the activity of which increases with an increase in the internal concentration of Na + ions and an increase in the external concentration of K + ions. Thanks to the operation of the ion pump and the change in membrane permeability for Na + and K +, their concentration in the intra- and extracellular space is gradually restored.

The result of these processes is membrane repolarization: the internal contents of the cell again acquire a negative charge in relation to the outer surface of the membrane.

Trace negative potential is recorded during the period when NO + channels are inactivated and repolarization associated with the release of K + ions from the cell occurs more slowly than during the descending part of the action potential peak. This long-term preservation of the negativity of the outer surface of the excited area in relation to the non-excited one is called trace depolarization. Trace depolarization means that during this period the outer surface of the excitable formation has a less positive charge than at rest.

Trace positive potential corresponds to the period of increasing resting membrane potential, i.e. membrane hyperpolarization. During a trace positive potential, the outer surface of the cell is more positively charged than at rest. The trace positive potential is often called the trace hyperpolarization. It is explained by the long-term preservation of increased permeability for K + ions. As a result, a potential is established on the membrane equal to the equilibrium potential (for K + - 90 mV).

Changes in excitability during the development of excitation. By influencing stimuli of different strengths in different phases of the action potential, it is possible to trace how excitability changes during excitation. In Fig. 2.13" it is clear that the period of the local response is characterized by increased excitability (the membrane potential approaches the critical level of depolarization); during the depolarization phase, the membrane loses excitability (the cell becomes refractory), which is gradually restored during repolarization.

Highlight absolute refractory period, which in nerve cells lasts about 1 ms and is characterized by their complete inexcitability. The period of absolute refractoriness occurs as a result of almost complete inactivation (impermeability) of sodium channels and an increase in potassium conductance of the membrane. Even at rest, not all membrane channels are activated; 40% of them are in a state of inactivation. During depolarization, the number of inactivated channels increases and the peak of the action potential corresponds to the inactivation of all sodium channels.

As the membrane repolarizes, sodium channels are reactivated. This relative refractory period: an action potential can only occur when exposed to stronger (suprathreshold) stimuli.

IN period of negative trace potential the phase of relative refractoriness is replaced by a phase of increased (supernormal) excitability. During this period, the threshold of irritation is reduced compared to the initial value, since the membrane potential is closer to the critical value than at rest (Fig. 2.14).

The phase of trace hyperpolarization, caused by the residual release of potassium from the cell, on the contrary, is characterized by a decrease

Rice. 2.13.

A - components of the excitation wave: 1 - depolarization; 2 - repolarization; MP - membrane potential; mV - microvolt; MK - critical level of depolarization: a - duration of the threshold potential; b - action potential duration; c - trace negativity; r - trace positivity; B - changes in excitability in different phases of the excitation wave; EF - level of excitability at rest: a - increase in excitability during the period of threshold potential; b - drop in excitability to zero during the occurrence of an action potential (absolute refractoriness); c, - return of excitability to the initial level during trace negativity (relative refractoriness); c 2 - increase in excitability during the period of the end of trace negativity (exaltation or supernormality); c - the entire period of trace negativity; d - drop in excitability during the period of hyperpolarization (subnormality)

excitability. Since the membrane potential is greater than at rest, a stronger stimulus is required to “shift” it to the level of critical depolarization.

Thus, in the dynamics of the excitatory process, the ability of the cell to respond to stimuli changes, i.e. excitability.

Rice. 2.14.

The magnitude of the membrane potential: E 0 - at rest; - in the exaltation phase; E 2 - in the hyperpolarization phase. Threshold potential value: e 0 - at rest; e, - in the exaltation phase; e 2 - in the hyperpolarization phase

This is of great importance, because at the moment of greatest excitation (peak action potential) the cell becomes completely inexcitable, which protects it from death and damage.

• See: Leontyeva N.N., Marinova K.V. Decree. Op.
• Right there.

Action potential (AP)is an electrophysiological process expressed in the rapid fluctuation of membrane potential due to the movement of ions into and out of the cell and capable spread without decrement(no attenuation). PD ensures the transmission of signals between nerve cells, nerve centers and working organs; in muscles, the PD ensures the process of electromechanical coupling.

A. Characteristics of the action potential (AP). The PD is shown schematically in Fig. 1.3. The magnitude of the action potential ranges from 80-130 mV, the duration of the peak action potential of the nerve fiber is 0.5-1 ms, of the skeletal muscle fiber - up to 10 ms, taking into account the slowing down of depolarization at the end of it. Duration of cardiac muscle action potential, 300-400 ms. The amplitude of the action potential does not depend on the strength of stimulation - it is always maximum for a given cell under specific conditions: the action potential obeys the “all or nothing” law, but does not obey the law of force relations - the law of force. AP either does not occur at all when the cell is irritated, if it is small, or it occurs and reaches its maximum value if the irritation is threshold or superthreshold.

It should be noted that weak (subthreshold) irritation can cause local potential. It obeys the law of force - with increasing strength of the stimulus, its magnitude increases.

The PD consists of four phases:

1 - depolarization, i.e. disappearance of the cell charge - a decrease in the membrane potential to zero;

2 - inversion, i.e. a change in the charge of the cell to the opposite, when the inner side of the cell membrane is charged positively, and the outer - negatively (Latin shuegzyu - turning over);

3 - repolarization, i.e. restoration of the original charge of the cell, when the inner surface of the cell membrane is again charged negatively, and the outer surface is charged positively;

4 - trace hyperpolarization.

B. The mechanism of occurrence of PD. If the action of a stimulus on the cell membrane leads to the onset of development of AP, then the process of AP development itself causes phase changes in the permeability of the cell membrane, which ensures the rapid movement of Na + into the cell, and K + out of the cell. This is the most common variant of the occurrence of PD. In this case, the value of the membrane potential first decreases and then restores again to its original level.

On the oscilloscope screen, the marked changes in the membrane potential appear in the form of peak potential - PD. It arises as a result of ion concentration gradients accumulated and maintained by ion pumps inside and outside the cell, i.e. due to potential energy in the form of electrochemical ion gradients. If you block the process of energy production, action potentials will occur for a certain period of time. But after the disappearance of ion concentration gradients (elimination of potential energy), the cell will not generate AP. Let's consider the phases of PD.

1. Depolarization phase(see Fig. 1.3 - 1). When a depolarizing stimulus acts on a cell (mediator, electric current), the initial partial depolarization of the cell membrane occurs without changing its permeability to ions. When depolarization reaches approximately 50% of the threshold value (50% of the threshold potential), the permeability of the cell membrane to Na + begins to increase, and at the first moment it is relatively slow.

Naturally, the rate of Na+ entry into the cell is low. During this period, as during the entire first phase (depolarization), driving force ensuring the entry of Hch!a + into the cell are concentration and electrical gradients. Let us remember that the inside of the cell is negatively charged (opposite charges attract each other), and the concentration of Na + outside the cell is 10-12 times greater than inside the cell.

Condition, ensuring the entry of Na + into the cell is an increase in the permeability of the cell membrane, which is determined by the state of the gate mechanism of Na channels (in some cells, for example, in cardiomyocytes, in smooth muscle fibers, an important role in the occurrence of APs is played and Ca 2+ gated channels).

When cell depolarization reaches a critical value (E, critical level of depolarization - CLD), which is usually 50 mV (other values ​​are possible), the permeability of the membrane for Na* increases sharply - a large number of voltage-dependent gates of Na channels open - and Na + rushes forward in an avalanche - gets into the cage.

As a result of the intense current of Na + into the cell, the depolarization process occurs very quickly. The developing depolarization of the cell membrane causes additional an increase in its permeability and, naturally, Na+ conductivity - more and more gates of Na-channels open, which gives the Na+ current into the cell its character regenerative process. As a result, the PP disappears and becomes equal to zero. The depolarization phase ends here.

2. Inversion phase. After the disappearance of the PP, the entry of Na+ into the cell continues, therefore the number of positive ions in the cell exceeds the number of negative ions, the charge inside the cell becomes positive, and outside - negative. The process of membrane recharging represents the second phase of the action potential - the inversion phase (Fig. 1.3 - 2).

Now the electrical gradient prevents Na+ from entering the cell (positive charges repel each other), Na-conductivity decreases. However, for a certain period of time (fractions of a millisecond) N+ continues to enter the cell - this is evidenced by the continuing increase in AP. This means that the concentration gradient that ensures the movement of Na+ into the cell is stronger than the electrical gradient that prevents Na+ from entering the cell.

During depolarization of the membrane, its permeability for Ca 2+ also increases; it also enters the cell, but in nerve fibers, neurons and skeletal muscle cells the role of Ca 2+ in the development of AP is small. In smooth muscle and myocardial cells, its role is significant. Thus, the entire ascending part of the AP peak in most cases is provided mainly by the entry of N+ into the cell.

Approximately 0.5-1 ms or more after the onset of depolarization (this time depends on the type of cell), the growth of AP stops due to the closing of the gates of sodium channels and the opening of the gates of K channels, i.e., an increase in permeability for K + and a sharp increase its exit from the cell (see Fig. 1.3 - 2). The growth of the AP peak is also prevented by the electrical gradient Na+ (the cell inside is positively charged at this moment), as well as the release of K+ from the cell through leakage channels.

Since K+ is located predominantly inside the cell, it, according to the concentration gradient, quickly leaves the cell after the K+ channel gate opens, as a result of which the number of positively charged ions in the cell decreases. The cell's charge begins to decrease again. During the inversion phase, the release of K+ from the cell is also facilitated by the electrical gradient. K+ is pushed out of the cell by the positive charge and attracted by the negative charge from outside the cell.

This continues until the positive charge inside the cell completely disappears (until the end of the inversion phase - Fig. 1.3-2, dotted line), when the next AP phase begins - the repolarization phase. Potassium leaves the cell not only through controlled channels, the gates of which are open, but also through uncontrolled channels - leakage channels, which somewhat slows down the progress of the ascending part of the AP and accelerates the progress of the descending component of the AP.

Thus, a change in the resting membrane potential leads to the sequential opening and closing of electrically controlled gates of ion channels and the movement of ions according to the electrochemical gradient - the emergence of AP. All phases are regenerative - it is only necessary to achieve a critical level of depolarization, then the AP develops due to the potential energy of the cell in the form of electrochemical gradients, i.e., secondary active.

The AP amplitude consists of the PP value (membrane potential of a resting cell) and the inversion phase value, which is 10-50 mV in different cells. If the membrane potential of a resting cell is small, the AP amplitude of this cell is small.

3. Repolarization phase(Fig. 1.3-3) is due to the fact that the permeability of the cell membrane for K + is still high (the potassium channel gates are open), K + continues to quickly leave the cell, according to the concentration gradient. Since the cell now again has a negative charge inside, and a positive charge outside (see Fig. 1.3 - 3), the electrical gradient prevents K + from leaving the cell, which reduces its conductivity, although it continues to leave.

This is explained by the fact that the effect of the concentration gradient is much stronger than the electrical gradient. The entire descending part of the AP peak is due to the release of K+ from the cell. Often, at the end of AP, a slowdown in repolarization is observed, which is explained by a decrease in the permeability of the cell membrane to K + and a slowdown in its release from the cell due to the partial closure of the K-channel gate. The second reason for the slowdown in the K+ current from the cell is associated with an increase in the positive potential of the outer surface of the cell and the formation of an oppositely directed electrical gradient.

Thus, plays a major role in the occurrence of PD Yа + , entering the cell when the permeability of the cell membrane increases and providing the entire ascending part of the AP peak. When replacing Ma + in the medium with another ion, for example choline, PD does not occur in the nerve and muscle cells of skeletal muscles. However, membrane permeability to K+ also plays an important role. If the increase in K + permeability is prevented by tetraethylammonium, the membrane, after its depolarization, repolarizes much more slowly, only due to slow uncontrolled channels (ion leak channels) through which K + will leave the cell.

Role of Ca 2+ in the occurrence of PD in nerve and muscle cells of skeletal muscles is insignificant. However, Ca 2+ plays an important role in the occurrence of action potential of cardiac and smooth muscles, in the transmission of impulses from one neuron to another, from nerve fiber to muscle fiber, and in ensuring muscle contraction.

4. Trace hyperpolarization cell membrane (Fig. 1.3-4) is usually a consequence of the still remaining increased permeability of the cell membrane to K +, it is characteristic of neurons. The K channel gate is not yet completely closed, so K+ continues to leave the cell according to the concentration gradient, which leads to hyperpolarization of the cell membrane.

Gradually, the permeability of the cell membrane returns to its original state (sodium and potassium gates return to their original state), and the membrane potential becomes the same as it was before the cell was excited. The Na/K pump is not directly responsible for the phases of the action potential, although it continues to work during the development of PD.

Trace depolarization Also characteristic of neurons, it can also be recorded in skeletal muscle cells. Its mechanism has not been sufficiently studied. This may be due to a short-term increase in the permeability of the cell membrane for Na + and its entry into the cell according to concentration and electrical gradients.

IN. The supply of ions in the cell, ensuring the occurrence of excitation (AP) is enormous. The concentration gradients of ions as a result of one excitation cycle practically do not change. The cell can be excited up to 510 5 times without recharging, that is, without the operation of the Na/K pump.

The number of impulses that a nerve fiber generates and conducts depends on its thickness, which determines the supply of ions. The thicker the nerve fiber, the greater the supply of ions and the more impulses it can generate (from several hundred to several hundred thousand) without the participation of the Na/K pump. However, in thin C-fibers, about 1% of the concentration gradients of Na + and K + are consumed for the occurrence of one AP.

Thus, if energy production is blocked, the cell will be excited many times again in this case. In reality, the Na/K pump constantly transports Na + from the cell, and returns K + to the cell, as a result, the concentration gradient of Na + and K + is constantly maintained, which is carried out due to the direct consumption of energy, the source which is ATP.

Action potential (AP)- these are short-term high amplitudes and changes in MPS that occur during excitation. The main cause of PD is a change in the permeability of the membrane to ions.
Let us consider the development of AP using the example of a nerve fiber. PD can be recorded by introducing one of the electrodes into the fiber or by placing both electrodes on its surface. Let us trace the process of AP formation using the intracellular method.
1. At rest, the membrane is polarized and the MVC is 90 mV.
2. As soon as excitation begins, the magnitude of this potential decreases (this decrease is called depolarization). In some cases, the potential of the sides of the membrane changes to the opposite (the so-called overshoot). This is the first stage of AP - depolarization.
3. The stage of repolarization, at which the magnitude of the potential difference drops almost to the original level. These two phases are in peak PD.
4. After the peak, trace potentials are observed - trace depolarization and trace hyperpolarization (hyperpolarization - an increase in the potential difference between the sides of the membrane). For example, it was 90 mV, but it becomes 100 mV.
PD develops very quickly - in a few milliseconds. PD parameters: 1) variable in nature, since the direction of current movement changes, 2) a value that, thanks to overshoot, can exceed the MVC; 3) the time during which AP and its individual stages develop - depolarization, repolarization, and subsequent hyperpolarization.
How is PD formed? In the resting state, the “gate” of voltage-gated Na + channels is closed. The “gates” of voltage-dependent K + channels are also closed.
1. During the depolarization phase, Na + -channel activation occurs. In this case, the conformational state of the proteins that make up the “gate” changes. These “gates” open, and the permeability of the membrane to Na + increases several thousand times. Na+ lava enters the nerve fiber. Currently, K+ channels open very slowly. Thus, significantly more Na + enters the fiber than K + is removed from it.
2. Repolarization is characterized by the closure of Na + channels. The “gate” on the inner surface of the membrane closes - inactivation of the channels under the influence of electrical potentials is observed. Inactivation occurs more slowly than activation. Currently, the activation of K + channels is accelerating and the outward diffusion of K + is increasing.
Thus, depolarization is associated primarily with the entry of Na + into the fiber, and repolarization is associated with the exit of K + from it. The ratio between the input of Na + and the output of K + changes during the process of one turn of the PD: at the beginning of the PD, several thousand times more Na + enters than K + is obtained, and then more K + comes out than Na + enters.
The cause of trace potentials is further changes in the relationship between these two processes. During trace hyperpolarization, many K+ channels still remain open and K+ continues to leak out.
Restoration of ion gradients after PD. Single APs change the difference in ion concentrations in the nerve fiber and outside it very little. But in cases where a significant number of pulses pass, this difference can be quite significant.
The restoration of ion gradients then occurs due to increased work of Na + / K + -HacociB - the more this gradient is disrupted, the more intense the pumps work. This uses the energy of ATP. Some of it is released in the form of heat, so in these cases there is a short-term increase in the temperature of the fiber.
Conditions necessary for the occurrence of PD. PD occurs only under certain conditions. The irritants acting on the fibers can be different. Direct electric current is most often used. It is easily dosed, causes little damage to tissue and is close to those irritants that exist in living organisms.
Under what conditions can direct current increase the appearance of PD? The current must be strong enough, act for a certain time, and its increase must be rapid. Finally, the direction of the current (action of the anode or cathode) also matters.
Depending on the strength, a distinction is made between subthreshold (insufficient to cause excitation), threshold (sufficient) and suprathreshold (excessive) current.
Despite the fact that the subthreshold current does not cause excitation, it still depolarizes the membrane, and this depolarization is greater, the higher its voltage.
The depolarization that develops in this case is called a local response and is a type of local excitation. It is characterized by the fact that it does not spread, its magnitude depends on the strength of irritation (the shutter of force relations: the greater the strength of irritation, the more active the response). With a local response, tissue excitability increases. Excitability is the ability to respond to irritation and move into a state of excitement.
If the strength of the stimulus is sufficient (threshold), then depolarization reaches a certain value, called the critical level of depolarization (Ek). For a nerve fiber covered with myelin, Ec is about 65 mV. Thus, the difference between the MPS (E0), equal in this case to 90 mV, and Ek is 25 mV. This value (DE = E0-Ek) is very important for characterizing tissue excitability.
When E0 increases with depolarization, excitability is higher and, conversely, a decrease in E0 with hyperpolarization leads to its decrease. WHERE may depend not only on the value of E0, but also on the critical level of depolarization (Ek).
At the threshold strength of the stimulus, AP occurs. This is no longer local excitation, it is capable of spreading over long distances and is subject to the “all or nothing” law (as the strength of the stimulus increases, the AP amplitude does not increase). Excitability during the development of PD is absent or significantly reduced.
PD is one of the indicators of excitation - an active physiological process with which living cells (nerve, muscle, glandular) respond to irritation. During excitation, metabolism and cell temperature change, the ionic balance between the cytoplasm and the external environment is disrupted, and a number of other processes occur.
In addition to the strength of the direct current, the occurrence of PD also depends on the duration of its action. There is an inverse proportional relationship between the strength of the current and the duration of its action. A subthreshold current, even with very long exposure, will not cause excitation. A suprathreshold current with too short an action will also not lead to excitation.
For excitation to occur, a certain rate (slope) of current increase is also required.
If you increase the current very slowly, then Ek will change and E0 may not reach its level.
The direction of the current also matters: PD occurs when the current closes only when the cathode is placed on the outer surface of the membrane and the anode is placed in a cell or fiber. When current passes, the MP changes. If the cathode lies on the surface, then depolarization develops (excitability increases), and if the anode - hyperpolarization (excitability decreases). Knowledge of the mechanisms of action of electric current on living objects is extremely necessary for the development and clinical application of physical therapy methods (diathermy, UHF, hyperhidrosis, etc.).
Changes in excitability during PD. With a local response, excitability increases (DE decreases). Changes in excitability during the AP itself can be noticed if the stimulation is repeated at different stages of AP development. It turns out that during the peak, even very strong repeated stimulation remains unanswered (period of absolute refractoriness). Then excitability gradually normalizes, but it is still lower than the initial one (relative refractory period).
With pronounced trace depolarization, excitability is higher than the initial one, and with a positive trace potential, excitability decreases again. Absolute refractoriness is explained by inactivation of Na + channels and increased conductivity of K + channels. With relative refractoriness, Na + channels are activated again and the activity of K + channels decreases.
Biphasic nature of PD. Typically, under conditions where the microelectrode is contained within a cell or fiber, a single-phase AP is observed. A different picture occurs in cases where both electrodes lie on the outer surface of the membrane - bipolar recording. The excitation, which is a wave of electronegativity, moving along the membrane, first reaches one electrode, then is placed between the electrodes, finally reaches the second electrode, and then spreads further. Under these conditions, the PD has a two-phase character. PD registration is widely used in the clinic for diagnosis

(RP) are short-term amplitude changes in the resting membrane potential (RMP) that occur when a living cell is excited. Essentially, this is an electrical discharge - a rapid, short-term change in potential in a small area of ​​the membrane of an excitable cell (neuron or muscle fiber), as a result of which the outer surface of this area becomes negatively charged in relation to neighboring areas of the membrane, while its inner surface becomes positively charged in relation to to adjacent areas of the membrane. The action potential is the physical basis of a nerve or muscle impulse that plays a signaling (regulatory) role.

general characteristics

Action potentials can differ in their parameters depending on the type of cell and even on different parts of the membrane of the same cell. The most typical example of differences is the action potential of the heart muscle and the action potential of most neurons. Nevertheless, the basis of any action potential is the following phenomena:

1. “The membrane of a living cell is polarized”- its inner surface is charged negatively in relation to the outer one due to the fact that in the solution at its outer surface there is a larger number of positively charged particles (cations), and at the inner surface there is a larger number of negatively charged particles (anions).
2. “The membrane has selective permeability ‘- its permeability to various particles (atoms or molecules) depends on their size, electrical charge and chemical properties.
3. “The membrane of an excitable cell is capable of quickly changing its permeability ‘for a certain type of cations, causing a transition of positive charge from the outside to the inside

The first two properties are characteristic of all living cells. The third is a feature of excitable tissue cells and the reason why their membranes are able to generate and conduct action potentials.

The main mathematical model describing the generation and transmission of action potentials is the Hodgkin-Huxley model.

Phases

Five phases of development of PD can be clearly distinguished:

Rising (depolarization)

The occurrence of an action potential (AP) is associated with an increase in the permeability of the membrane for sodium ions (20 times compared to the permeability for K +, and 500 times compared to the initial permeability of Na +) and a subsequent increase in the diffusion of these ions along the concentration gradient into the cell, leads to a change (decrease) in membrane potential. A decrease in membrane potential leads to an increase in membrane permeability to sodium by opening voltage-gated sodium channels, and an increase in permeability is accompanied by increased diffusion of sodium into the cytoplasm, which causes even more significant depolarization of the membrane. Due to the presence of positive feedback, depolarization of the membrane during excitation occurs with acceleration and the flow of sodium ions into the cell increases all the time. The intensity of the flow of potassium ions directed from the cell outwards in the first moments of excitation remains at the beginning. The increased flow of positively charged sodium ions into the cell first causes the disappearance of excess negative charge on the inner surface of the membrane, and then leads to recharging of the membrane. The influx of sodium ions occurs until the inner surface of the membrane acquires a positive charge sufficient to balance the sodium concentration gradient and stop its further passage into the cell. The sodium occurrence of PD is confirmed by experiments with changes in the external and internal concentrations of this ion. It was shown that a tenfold change in the concentration of sodium ions in the external or internal environment of the cell corresponds to a change in PD of 58 mV. When sodium ions were completely removed from the fluid surrounding the cell, PD did not occur. Thus, it has been established that AP occurs as a result of excess, compared to rest, diffusion of sodium ions from the surrounding fluid into the cell. The period during which the membrane permeability for sodium ions increases when sodium channels open is short (0.5-1 ms), followed by an increase in membrane permeability for potassium ions due to the opening of voltage-dependent potassium channels, and, consequently, increased diffusion these ions out of the cell.

Overshoot

Depolarization of the membrane leads to a reversal of the membrane potential (the MP becomes positive). In the overshoot phase, the Na + current begins to rapidly decrease, which is associated with the inactivation of voltage-dependent Na + channels (the open state time is milliseconds) and the disappearance of the electrochemical Na + gradient.

Repolarization

An increase in the potassium ion flow directed outward from the cell leads to a decrease in the membrane potential, which in turn causes a decrease in the permeability of the membrane to sodium ions, which, as indicated, is a function of the membrane potential. Thus, the second stage is characterized by the fact that the flow of potassium ions from the cell outward increases, and the counter flow of sodium ions decreases. This membrane repolarization continues until the resting potential is restored—membrane repolarization. After this, the permeability to potassium ions also drops to its original value. Due to the positively charged potassium ions released into the environment, the outer surface of the membrane again acquires a positive potential relative to the internal one.

Trace depolarization and hyperpolarization

In the final phase, the restoration of the resting membrane potential slows down, and trace reactions are recorded in the form of trace depolarization and hyperpolarization, due to the slow restoration of the initial permeability for K + ions.

Spreading

Spread into unmyelinated fibers

In unmyelinated (without pulp) nerve fibers, the AP spreads from point to point, since excitation can be registered as one that gradually “runs” along the entire fiber from its point of origin. Sodium ions entering the excited area serve as a source of electric current for the occurrence of AP in adjacent areas. In this case, the impulse occurs between the depolarized section of the membrane and its non-excited section. The potential difference here is many times higher than necessary for membrane depolarization to reach the maximum level. The speed of pulse propagation in such fibers is 0.5-2 m/s

Spread in myelinated fibers

The nerve processes of most somatic nerves are myelinated. Only very small areas of them, the so-called node interception (interception of Ranvier), are covered with a normal cell membrane. Such nerve fibers are characterized by the fact that voltage-dependent ion channels are located on the membrane only at the interceptions. In addition, this shell increases the electrical resistance of the membrane. Therefore, when the membrane potential shifts, the current passes through the membrane of the intercepting area, that is, by jumping (saltatory) from one interception to another, which allows you to increase the speed of the nerve impulse, which ranges from 5 to 120 m/s. Moreover, the action potential that arose in one of the nodes of Ranvier causes action potentials in neighboring nodes due to the emergence of an electric field, which causes an initial depolarization in these nodes. The parameters of the EMF field and the distance of its effective action depend on the cable properties of the axon.

Action potential propagation between cells

At a chemical synapse, after the action potential wave reaches the nerve terminal, it causes the release of neurotransmitters from the presynaptic vesicles into the synaptic cleft. Transmitter molecules released from the presynapse bind to receptors on the postsynaptic membrane, resulting in the opening of ion channels in the receptor macromolecules. Ions begin to enter the postsynaptic cell through open channels, change the charge of its membrane, which leads to partial depolarization of the membrane and, as a consequence, provoking the generation of an action potential in the postsynaptic cell.

In the electrical synapse there is no “mediator” of transmission in the form of a neurotransmitter. But the cells are connected to each other using specific protein tunnels - conexons, so ionic currents from the presynaptic cell can stimulate the postsynaptic cell, causing the generation of an action potential in it. Thanks to this structure, the action potential can propagate in both directions and much faster than through a chemical synapse.

Scheme of the process of nerve signal transmission at a chemical synapse

Diagram of the structure of an electrical synapse

Action potential in different cell types

Action potential in muscle tissue

The action potential in skeletal muscle cells is similar to the action potential in neurons. Their resting potential is typically -90 mV, which is less than the resting potential of typical neurons. The action potential of muscle cells lasts approximately 2–4 ms, the absolute refractory period is approximately 1–3 ms, and the conduction velocity along the muscle is approximately 5 m/s.

Action potential in cardiac tissue

The action potential of the cells of the working myocardium consists of a phase of rapid depolarization, an initial rapid repolarization, which turns into a phase of slow repolarization (plateau phase), and a phase of rapid final repolarization. The phase of rapid depolarization is caused by a sharp increase in the permeability of the membrane for sodium ions, causes a rapid incoming sodium current, when the membrane potential reaches 30-40 mV it is inactivated and subsequently the calcium ion current plays a major role. Depolarization of the membrane causes activation of calcium channels, resulting in an additional depolarizing incoming calcium current.

The action potential in cardiac tissue plays an important role in coordinating cardiac contractions.

Molecular mechanisms of action potential generation

The active properties of the membrane that ensure the occurrence of an action potential, based mainly on the behavior of voltage-gated sodium (Na +) and potassium (K +) channels. The initial phase of AP is formed by the input sodium current, later potassium channels open and the output K + -current returns the membrane potential to the initial level. The initial ion concentration is then restored by the sodium-potassium pump.

During the PD, channels pass from state to state: in Na + channels there are three main states - closed, open and inactivated (in reality everything is more complicated, but these three states are enough for description), in K + channels there are two - closed and open.

The behavior of the channels involved in the formation of PD is described in terms of conductivity and calculated through transfer coefficients.

Carryover coefficients were derived by Alan Lloyd Hodgkin and Andrew Huxley.

Conductivity for potassium G K per unit area Conductivity for sodium G Na per unit area

it is more difficult to calculate, since, as already mentioned, in voltage-dependent Na + channels, in addition to closed / open states, the transition between which is a parameter, there are also inactivated / not inactivated states, the transition between which is described through a parameter

Research methods

Story

The main provisions of the membrane theory of excitation were formulated by the German neurophysiologist Yu. Bernstein

In 1902, Julius Bernstein put forward a hypothesis according to which the cell membrane allows K+ ions into the cell, and they accumulate in the cytoplasm. The calculation of the resting potential value using the Nernst equation for the potassium electrode satisfactorily coincided with the measured potential between the muscle sarcoplasm and the environment, which was about -70 mV. According to the theory of Yu. Bernstein, when a cell is excited, its membrane is damaged, and K + ions leave the cell along a concentration gradient until the membrane potential becomes zero. The membrane then restores its integrity and the potential returns to the resting potential level.

This model was developed in their 1952 work by Alan Lloyd Hodgkin and Andrew Huxley, in which they described the electrical mechanisms responsible for the generation and transmission of a nerve signal in the squid giant axon. For this, the authors of the model received the Nobel Prize in Physiology or Medicine for 1963. The model is called the Hodgkin-Huxley model

In 2005, Thomas Heimburg and Andrew D. Jackson proposed the soliton model, based on the assumption that the signal propagates through neurons in the form of solitons - stable waves propagating along the cell membrane.

The effect of certain substances on the action potential

Some substances of organic or synthetic origin can block the formation or passage of PD:

• Batrachotoxin has been found in some representatives of the leaf climber genus. Sustainably and irreversibly increases the permeability of membranes to sodium ions.
• Poneratoxin was found in ants of the genus Paraponera. Blocks sodium channels.
• Tetrodotoxin was found in the tissues of fish of the Skelezubovi family, from which the Japanese delicacy Fugu is prepared. Blocks sodium channels.
• The mechanism of action of most anesthetics (Procaine, Lidocaine) is based on blocking sodium channels and, accordingly, blocking the conduction of impulses along sensitive nerve fibers.
• 4-Aminopyridine - reversely blocks potassium channels, prolongs the duration of the action potential. Can be used in the treatment of multiple sclerosis.
• ADWX 1 - reversely blocks potassium channels. Under experimental conditions, it alleviated the course of acute disseminated encephalomyelitis in rats.

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