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.
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 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.
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 certain 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 particular 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 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. 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.
Biological membrane, membrane thickness 7-10 nm, consists of a double layer of phospholipids: hydrophilic parts (heads) are directed to the membrane surface; hydrophobic parts (tails) are directed inside the membrane. Hydrophobic ends stabilize the membrane in the form of a bilayer
FUNCTIONS OF MEMBRANES STRUCTURAL STRUCTURAL. PROTECTIVE.PROTECTIVE. ENZYMATIVE ENZYMATIVE CONNECTIVE OR ADHESIVE (causes the existence of multicellular organisms). RECEPTOR RECEPTOR. ANTIGENIC ANTIGENIC. ELECTROGENIC ELECTROGENIC TRANSPORT TRANSPORT.
COMMUNICATION BETWEEN CELLS CELL signaling molecule (first messenger) or ligand CELL signaling molecule (first messenger) or ligand membrane molecule (channel or receptor) membrane molecule (channel or receptor) TARGET CLECTS cell molecules or second messengers cascade of enzymatic reactions change in cell function CLECTIES -TARGETS cell molecules or second mediators cascade of enzymatic reactions change in cell function
MEMBRANE RECEPTORS These are molecules (proteins, glyco- or lipoproteins) that are sensitive to biologically active substances - ligands These are molecules (proteins, glyco- or lipoproteins) that are sensitive to biologically active substances - ligands Ligands - external stimuli for the cell Ligands - external stimuli for the cell Receptors - highly specific or selective Receptors - highly specific or selective
MECHANISM OF OPERATION OF RECEPTORS Membrane receptors register the presence of a ligand: they transmit a signal to intracellular chemical compounds to the second intermediaries - MESSENGER 2. 2. Regulate the state of ion channels
PROPERTIES OF ION CHANNELS 1. Selectivity - 1. Selectivity - each channel passes only a certain ("own") ion It can be in different functional states: closed, but ready to open (1) open - activated (2) Inactivated (3)
Hyperpolarization Increase in AP difference between membrane sides Increase in AP difference between membrane sides
RESTING MEMBRANE POTENTIAL This is the potential difference between the outer and inner surface of the membrane of an excitable cell at rest. The resting potential is recorded by the intracellular microelectrode in relation to the reference extracellular electrode.
Gradient This is a vector that shows the difference between the largest and smallest value of a quantity at different points in space, and also indicates the degree of this change. This is a vector that shows the difference between the largest and smallest value of a quantity at different points in space, and also indicates the degree of this change.
FACTORS FORMING MT 1. IONIC ASYMETRY Potassium concentration gradient Potassium concentration gradient Sodium concentration gradient Sodium concentration gradient = p = 8-10p
2. Semipermeability of the membrane K + Na + Cl - Protein
"Electrical Gradient" This is the force created by the electric field of the transmembrane potential difference This is the force created by the electric field of the transmembrane potential difference The release of potassium to the outside reduces the concentration gradient, and the electric one increases it. The release of potassium to the outside reduces the concentration gradient, while the electric one increases it. As a result, the magnitude of the gradients is leveled As a result, the magnitude of the gradients is leveled
"Electric Gradient" A transmembrane potential difference creates an electric field, and hence an electric gradient A transmembrane potential difference creates an electric field, and hence an electric gradient As potassium escapes, the concentration gradient decreases and the electric gradient increases. As potassium is released to the outside, the concentration gradient decreases, and the electric gradient increases. As a result, the two gradients equalize The result, the two gradients equalize
Equilibrium potential equilibrium state is such a value of the electric charge of the membrane, which completely balances the concentration gradient for a particular ion and the total current of this ion will be equal to 0. The equilibrium state is such a value of the electric charge of the membrane, which completely balances the concentration gradient for a certain ion and the total current this ion will be equal to 0. Equilibrium potential for potassium = -86 mV (Ek+ = -86 mV) Equilibrium potential for potassium = -86 mV (Ek+ = -86 mV)
The resting state of the cell The membrane is slightly permeable to sodium, which reduces the charge difference and the magnitude of the electrical gradient The membrane is slightly permeable to sodium, which reduces the magnitude of the charge difference and the magnitude of the electrical gradient Potassium leaves the cell Potassium leaves the cell
Mechanisms for maintaining ion asymmetry Electric charge on the membrane - promotes the entry of potassium into the cell and inhibits its exit Electric charge on the membrane - promotes the entry of potassium into the cell and inhibits its exit Potassium-sodium pump is an active transport that transports ions across the membrane against the concentration gradient sodium pump - active transport that transports ions across the membrane against a concentration gradient
FUNCTIONS OF THE POTASSIUM-SODIUM PUMP Active ion transport Active ion transport ATPase enzymatic activity ATPase enzymatic activity Maintenance of ionic asymmetry Maintenance of ionic asymmetry Increased membrane polarization - electrogenic effect Increased membrane polarization - electrogenic effect
Depolarization Occurs when sodium channels open Occurs when sodium channels open Sodium enters the cell: Sodium enters the cell: reduces the negative charge on the inner surface of the membrane reduces the negative charge on the inner surface of the membrane reduces the electric field around the membrane reduces the electric field around the membrane The degree of depolarization depends on the amount open channels for sodium The degree of depolarization depends on the number of open channels for sodium
CRITICAL LEVEL OF DEPOLARIZATION Е cr The level of depolarization at which the maximum possible number of sodium channels opens (all channels for sodium are open) The level of depolarization at which the maximum possible number of sodium channels opens (all channels for sodium are open) The flow of sodium ions "avalanche" rushes into the cell The flow of sodium ions "avalanche" rushes into the cell Regenerative depolarization begins Regenerative depolarization begins
Depolarization threshold The difference between the value of the initial polarization of the membrane (E 0) and the critical level of depolarization (E cr) The difference between the value of the initial polarization of the membrane (E 0) and the critical level of depolarization (E cr) Δ V= E 0 - E cr Δ V= E 0 - E cr In this case, the current of sodium exceeds the current of potassium by 20 times! In this case, the current of sodium exceeds the current of potassium by 20 times! Depends on the ratio of activated sodium and potassium channels Depends on the ratio of activated sodium and potassium channels
The law of "all or nothing" Subthreshold stimulus causes local depolarization ("nothing") Subthreshold stimulus causes local depolarization ("nothing") Threshold stimulus causes the maximum possible response ("All") Threshold stimulus causes the maximum possible response ("All") Suprathreshold stimulus causes the same response as the threshold Suprathreshold stimulus causes the same response as the threshold T.o. the response of the cell does not depend on the strength of the stimulus. That. the response of the cell does not depend on the strength of the stimulus.
LO Properties of LO 1. It does not follow the “all or nothing” law The amplitude of LO depends on the strength of the stimulus It spreads along the membrane by attenuation (decrement) It can be summed up (as a result, the amplitude of depolarization increases) Transforms into an action potential when the level of critical depolarization is reached
Action potential (AP) This is the potential difference between the excited and unexcited areas of the membrane, which occurs as a result of rapid depolarization of the membrane, followed by its recharge. This is the potential difference between the excited and unexcited sections of the membrane, which occurs as a result of the rapid depolarization of the membrane, followed by its recharging. AP amplitude is about 120 - 130 μV, duration (on average) - 3 - 5 ms AP amplitude is about 120 - 130 μV, duration (on average) - 3 - 5 ms (in different tissues from 0.01 ms to 0.3 s) . (in different tissues from 0.01 ms to 0.3 s).
E0E0 E cr mV
Conditions for the occurrence of AP Depolarization must reach a critical level of depolarization Depolarization must reach a critical level of depolarization The sodium current into the cell must exceed the potassium current from the cell by 20 times (the channels for sodium are fast-conducting, and for potassium they are slow) The sodium current into the cell must exceed the potassium current from the cell by 20 times (channels for sodium are fast-conducting, and for potassium - slow) Regenerative depolarization should develop Regenerative depolarization should develop
E0E0 E cr 0 +30
Irritation This is the process of influencing the cell This is the process of influencing the cell The effect of the effect depends both on the qualitative and quantitative characteristics of the stimulus, and the properties of the cell itself The effect of the effect depends on both the qualitative and quantitative characteristics of the stimulus, and the properties of the cell itself
LAWS OF IRRITATION This is a set of rules describing the requirements that a stimulus must obey in order for it to cause a process of excitation. These include: the polar law the law of force the law of time (duration of action) the law of steepness (time of force rise)
69 Laws of irritation The law of force The law of force - in order for PD to occur, the strength of the stimulus must be no less than the threshold value. The law of time The law of time - for AP to occur, the duration of the stimulus must be at least the threshold value
The dependence of the force on the action time P - rheobase - this is the minimum current strength that causes excitation PV - useful time - the minimum time of action of an irritating impulse with a force of one rheobase necessary for excitation. Хр - chronascuia - the minimum duration of the action of an irritating impulse with a force of 2 rheobases, necessary for the recurrence of AP.
Accommodation This is the ability of a tissue to adapt to a long-acting stimulus. At the same time, its strength also increases slowly (small steepness). This is the ability of the tissue to adapt to a long-acting stimulus. At the same time, its strength also increases slowly (small steepness) The critical level of depolarization shifts towards zero The critical level of depolarization shifts towards zero The sodium channels do not open simultaneously and the sodium current into the cell is compensated by the potassium current from the cell. PD does not occur, because no regenerative depolarization The sodium channels do not open simultaneously and the sodium current into the cell is compensated by the potassium current out of the cell. PD does not occur, because no regenerative depolarization Accommodation manifests itself in an increase in the threshold strength of the stimulus with a decrease in the steepness of the increase in the stimulus - the lower the steepness, the greater the threshold strength. The basis of tissue accommodation is the process of inactivation of sodium channels. Therefore, the lower the steepness of the stimulus rise, the more sodium channels are inactivated, the level of critical depolarization shifts and the threshold strength of the stimulus increases. If the steepness of the stimulus rise is less than the threshold value, then AP does not occur and only a local response will be observed.
ELECTROTONE PHYSIOLOGICAL Changes in the excitability of the membrane during prolonged exposure to direct current of subthreshold strength. catelectroton - At the same time, catelectroton develops under the cathode - an increase in excitability. anelectroton under the anode - anelectroton - a decrease in excitability.
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Cathodic depression according to Verigo If the constant current acts on the membrane for a long time, then the increased excitability under the cathode changes into a decrease in excitability. This phenomenon is based on the phenomenon of tissue accommodation, because direct current can be represented as a current with an infinitely small slope of rise.
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 conducted tissues, and using the example of the process of excitation of organic cells, we will 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 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 activation gate, has the ability to pass ions, the other is inactivation. 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 depolarization of the cell membrane is reached, the 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 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 established 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 "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), then 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 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 "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 exhibits 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 incoming current channel. In mammals, an available additional source of Ca 2+ for cardiac cells is its reserves in the sarcoplasmic reticulum.
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resting membrane potential (MPP) or resting potential (PP) is the potential difference of a resting cell between the inner and outer sides of the membrane. The inner side of the cell membrane is negatively charged relative to the outer. Taking the potential of the external solution as zero, the MPP is recorded with a minus sign. Value WFP depends on the type of tissue and varies from -9 to -100 mV. Therefore, at rest, the cell membrane polarized. A decrease in the MPP value is called depolarization increase - hyperpolarization, restoring the original value WFP- repolarization membranes.
The main provisions of the membrane theory of origin WFP come down to the following. At rest, the cell membrane is well permeable to K + ions (in some cells and to SG), less permeable to Na + and practically impermeable to intracellular proteins and other organic ions. K + ions diffuse out of the cell along a concentration gradient, while non-penetrating anions remain in the cytoplasm, providing the appearance of a potential difference across the membrane.
The resulting potential difference prevents the exit of K + from the cell, and at a certain value, an equilibrium occurs between the exit of K + along the concentration gradient and the entry of these cations along the resulting electrical gradient. The membrane potential at which this equilibrium is reached is called equilibrium potencyscarlet Its value can be calculated from the Nernst equation:
where E to- equilibrium potential for To + ; R- gas constant; T- absolute temperature; F - Faraday number; P- valency K + (+1), [K n +] - [K + vn] - external and internal concentrations of K + -
If we switch from natural logarithms to decimal logarithms and substitute the numerical values of the constants into the equation, then the equation will take the form: 
In spinal neurons (Table 1.1) E k = -90 mV. The MPP value measured using microelectrodes is noticeably lower, 70 mV.
Table 1.1. The concentration of some ions inside and outside the spinal motor neurons of mammals
| And he |
Concentration |
(mmol/l H 2 O) |
Weight potential (mV) |
|
inside the cell |
outside the cage |
||
| Na+ | 15,0 | 150,0 | |
| K+ | 150,0 | 5,5 | |
| Cl - | 125,0 | ||
|
Resting membrane potential = -70 mV |
|||
If the membrane potential of a cell is of a potassium nature, then, in accordance with the Nernst equation, its value should decrease linearly with a decrease in the concentration gradient of these ions, for example, with an increase in the concentration of K + in the extracellular fluid. However, a linear dependence of the RMP value (resting membrane potential) on the K + concentration gradient exists only at a K + concentration in the extracellular fluid above 20 mM. At lower concentrations of K + outside the cell, the dependence curve of E m on the logarithm of the ratio of potassium concentration outside and inside the cell differs from the theoretical one. It is possible to explain the established deviations of the experimental dependence of the MPP value and the K + concentration gradient theoretically calculated by the Nernst equation by assuming that the MPP of excitable cells is determined not only by potassium, but also by sodium and chloride equilibrium potentials. Arguing similarly to the previous one, we can write:
The values of sodium and chloride equilibrium potentials for spinal neurons (Table 1.1) are +60 and -70 mV, respectively. The value of E Cl is equal to the value of the MPP. This indicates a passive distribution of chloride ions through the membrane in accordance with chemical and electrical gradients. For sodium ions, the chemical and electrical gradients are directed inside the cell.
The contribution of each of the equilibrium potentials to the MPP value is determined by the ratio between the permeability of the cell membrane for each of these ions. The membrane potential value is calculated using the Goldman equation:
E m- membrane potential; R- gas constant; T- absolute temperature; F- Faraday number; RK, P Na and RCl- membrane permeability constants for K + Na + and Cl, respectively; [TO+ n ], [ K + ext, [ Na+ n [ Na + ext], [Cl - n] and [Cl - ext] - concentrations of K + , Na + and Cl outside (n) and inside (ext) of the cell.
Substituting into this equation the ion concentrations and the MPP value obtained in experimental studies, it can be shown that for the giant squid axon there should be the following ratio of the permeability constants Р to: P Na: Р С1 = I: 0.04: 0.45. Obviously, since the membrane is permeable to sodium ions (P N a =/ 0) and the equilibrium potential for these ions has a plus sign, then the entry of the latter into the cell along the chemical and electrical gradients will reduce the electronegativity of the cytoplasm, i.e. increase the MPP (membrane resting potential).
With an increase in the concentration of potassium ions in the external solution above 15 mM, the MPP increases and the ratio of the permeability constants changes towards a more significant excess of Pk over P Na and P C1. P c: P Na: P C1 = 1: 0.025: 0.4. Under such conditions, the MPP is determined almost exclusively by the gradient of potassium ions; therefore, the experimental and theoretical dependences of the MPP on the logarithm of the ratio of potassium concentrations outside and inside the cell begin to coincide.
Thus, the presence of a stationary potential difference between the cytoplasm and the external environment in a resting cell is due to the existing concentration gradients for K + , Na + and Cl and different membrane permeability for these ions. The main role in the generation of MPP is played by the diffusion of potassium ions from the cell into the outer lumen. Along with this, the MPP is also determined by the sodium and chloride equilibrium potentials, and the contribution of each of them is determined by the relationship between the permeabilities of the cell's plasma membrane for these ions.
All the factors listed above constitute the so-called ionic component RMP (membrane resting potential). Since neither potassium nor sodium equilibrium potentials are equal to MPP. the cell must absorb Na + and lose K + . The constancy of the concentrations of these ions in the cell is maintained by the work of Na + K + -ATPase.
However, the role of this ion pump is not limited to maintaining sodium and potassium gradients. It is known that the sodium pump is electrogenic and during its operation a net flow of positive charges arises from the cell into the extracellular fluid, which causes an increase in the electronegativity of the cytoplasm with respect to the environment. The electrogenicity of the sodium pump was revealed in experiments on giant mollusk neurons. Electrophoretic injection of Na + ions into the body of a single neuron caused membrane hyperpolarization, during which the MPP was significantly lower than the potassium equilibrium potential. This hyperpolarization was weakened by lowering the temperature of the solution in which the cell was located, and was suppressed by the specific inhibitor of Na + , K + -ATPase ouabain.
From what has been said, it follows that the MPP can be divided into two components - "ionic" and "metabolic". The first component depends on the concentration gradients of ions and membrane permeabilities for them. The second, "metabolic", is due to the active transport of sodium and potassium and has a dual effect on MPP. On the one hand, the sodium pump maintains concentration gradients between the cytoplasm and the environment. On the other hand, being electrogenic, the sodium pump has a direct effect on MPP. Its contribution to the MPP value depends on the density of the “pumping” current (current per unit area of the cell membrane surface) and the membrane resistance.
Membrane action potential
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If a nerve or muscle is irritated above the excitation threshold, then the MPP of the nerve or muscle will quickly decrease and for a short period of time (millisecond) the membrane will be recharged: its inner side will become positively charged relative to the outer. it a short-term change in the MPP that occurs when the cell is excited, which has the form of a single peak on the oscilloscope screen, is called membrane action potential (MPD).
MPD in the nervous and muscle tissues occurs when the absolute value of the MPP (membrane depolarization) decreases to a certain critical value, called generation threshold MTD. In the giant nerve fibers of the squid, the MPD is -60 mV. When the membrane is depolarized to -45 mV (the IVD generation threshold), IVD occurs (Fig. 1.15).
Rice. 1.15 The action potential of the nerve fiber (A) and the change in the conductivity of the membrane for sodium and potassium ions (B).During IVD initiation in the squid axon, the membrane resistance decreases by a factor of 25, from 1000 to 40 Ohm.cm2, while the capacitance does not change. This decrease in membrane resistance is due to an increase in the ion permeability of the membrane upon excitation.
In terms of its amplitude (100-120 mV), the MPD (Membrane Action Potential) is 20-50 mV higher than the value of the MPP (Resting Membrane Potential). In other words, the inner side of the membrane briefly becomes positively charged with respect to the outer side, "overshoot" or charge reversal.
It follows from the Goldmann equation that only an increase in the permeability of the membrane for sodium ions can lead to such changes in the membrane potential. The value of Ek is always less than the value of the MPP, so an increase in the permeability of the membrane for K + will increase the absolute value of the MPP. The sodium equilibrium potential has a plus sign, so a sharp increase in the membrane permeability for these cations leads to membrane recharging.
During IVD, the permeability of the membrane to sodium ions increases. Calculations have shown that if at rest the ratio of the membrane permeability constants for K + , Na + and SG is 1:0.04:0.45, then at IVD - Р to: P Na: Р = 1: 20: 0.45 . Consequently, in the state of excitation, the nerve fiber membrane not only loses its selective ion permeability, but, on the contrary, from being selectively permeable to potassium ions at rest, it becomes selectively permeable to sodium ions. An increase in the sodium permeability of the membrane is associated with the opening of voltage-dependent sodium channels.
The mechanism that provides opening and closing of ion channels is called channel gate. It is customary to distinguish activation(m) and inactivation(h) gate. The ion channel can be in three main states: closed (m-gates are closed; h-open), open (m- and h-gates are open) and inactivated (m-gates are open, h-gates are closed) (Figure 1.16).
Rice. 1.16 Scheme of the position of activation (m) and inactivation (h) gates of sodium channels, corresponding to closed (rest, A), open (activation, B) and inactivated (C) states.
Depolarization of the membrane, caused by an irritating stimulus, for example, an electric current, opens the m-gates of sodium channels (transition from state A to B) and provides the appearance of an inward flow of positive charges - sodium ions. This leads to further depolarization of the membrane, which in turn increases the number of open sodium channels and therefore increases the sodium permeability of the membrane. There is a "regenerative" depolarization of the membrane, as a result of which the potential of the inner side of the membrane tends to reach the value of the sodium equilibrium potential.
The reason for the cessation of the growth of IVD (Membrane Action Potential) and repolarization of the cell membrane is:
a) Increased membrane depolarization, i.e. when E m -» E Na, as a result of which the electrochemical gradient for sodium ions decreases, equal to E m -> E Na. In other words, the force "pushing" sodium into the cell decreases;
b) Depolarization of the membrane generates the process of inactivation of sodium channels (closing of the h-gate; state of the B channel), which inhibits the growth of sodium permeability of the membrane and leads to its decrease;
in) Depolarization of the membrane increases its permeability to potassium ions. The outgoing potassium current tends to shift the membrane potential towards the potassium equilibrium potential.
Decreasing the electrochemical potential for sodium ions and inactivating sodium channels reduces the amount of incoming sodium current. At a certain point in time, the value of the incoming sodium current is compared with the increased outgoing current - the growth of the MTD stops. When the total outgoing current exceeds the incoming one, membrane repolarization begins, which also has a regenerative character. The repolarization that has begun leads to the closing of the activation gate (m), which reduces the sodium permeability of the membrane, accelerates repolarization, and the latter increases the number of closed channels, etc.
The phase of IVD repolarization in some cells (for example, in cardiomyocytes and a number of smooth muscle cells) can slow down, forming plateau PD, due to complex changes in time of incoming and outgoing currents through the membrane. In the aftereffect of IVD, hyperpolarization and/or depolarization of the membrane may occur. These are the so-called trace potentials. Trace hyperpolarization has a dual nature: ionic and metabolickuyu. The first is related to the fact that the potassium permeability in the nerve fiber of the membrane remains elevated for some time (tens and even hundreds of milliseconds) after IVD generation and shifts the membrane potential towards the potassium equilibrium potential. The trace hyperpolarization after rhythmic stimulation of cells is associated mainly with the activation of the electrogenic sodium pump, due to the accumulation of sodium ions in the cell.
The reason for the depolarization that develops after the generation of the MPD (Membrane Action Potential) is the accumulation of potassium ions at the outer surface of the membrane. The latter, as it follows from the Goldman equation, leads to an increase in the RRP (Resting Membrane Potential).
The inactivation of sodium channels is associated with an important property of the nerve fiber calledrefractoriness .
During absofierce refractory period the nerve fiber completely loses the ability to be excited by the action of a stimulus of any strength.
Relative refractoriness, following the absolute, is characterized by a higher threshold for the occurrence of IVD (Membrane Action Potential).
The idea of membrane processes occurring during excitation of the nerve fiber serves as the basis for understanding and the phenomenon accommodation. At the basis of tissue accommodation with a small steepness of the rise of the irritating current is an increase in the excitation threshold, which is ahead of the slow depolarization of the membrane. The increase in the excitation threshold is almost entirely determined by the inactivation of sodium channels. The role of an increase in the potassium permeability of the membrane in the development of accommodation is that it leads to a drop in the resistance of the membrane. Due to the decrease in resistance, the rate of membrane depolarization becomes even slower. The rate of accommodation is the higher, the greater the number of sodium channels at the resting potential is in an inactivated state, the higher the rate of development of inactivation and the higher the potassium permeability of the membrane.
Carrying out excitation
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Conduction of excitation along the nerve fiber is carried out due to local currents between the excited and resting sections of the membrane. The sequence of events in this case is presented as follows.
When a point stimulation is applied to a nerve fiber, an action potential arises in the corresponding section of the membrane. The inner side of the membrane at a given point is positively charged with respect to the adjacent, resting side. Between the points of the fiber that have different potentials, a current arises (local current), directed from excited (sign (+) on the inside of the membrane) to unexcited (sign (-) on the inside of the membrane) to the fiber section. This current has a depolarizing effect on the fiber membrane in the resting area, and when the critical level of membrane depolarization is reached in this area, an MPD (Membrane Action Potential) occurs. This process consistently spreads to all parts of the nerve fiber.
In some cells (neurons, smooth muscles), IVD is not of a sodium nature, but is due to the entry of Ca 2+ ions through voltage-dependent calcium channels. In cardiomyocytes, IVD generation is associated with incoming sodium and sodium-calcium currents.
