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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 inside of the cell membrane is negatively charged relative to the outside. Taking the potential of the external solution as zero, the MPP is written with a minus sign. Magnitude MPP depends on the type of tissue and varies from -9 to -100 mV. Therefore, in a state of rest the cell membrane polarized. A decrease in the MPP value is called depolarization, increase - hyperpolarization, restoring the original value MPP- repolarization membranes.

Basic provisions of the membrane theory of origin MPP boil down to the following. In the resting state, the cell membrane is highly permeable to K + ions (in some cells and for 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, and 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 achieved is called equilibrium potencyscarlet Its value can be calculated from the Nernst equation:

Where E k- equilibrium potential for TO + ; R- gas constant; T- absolute temperature; F - Faraday number; P- valence K + (+1), [K n + ] - [K + in ] - external and internal concentrations of K + -

If you go from natural logarithms to decimal and substitute into the equation numeric values constants, 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. Concentrations of some ions inside and outside mammalian spinal motor neurons

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
Сl -		125,0
	Resting membrane potential = -70 mV

If the cell membrane potential is potassium in 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 when the K + concentration in the extracellular fluid is above 20 mM. At lower concentrations of K + outside the cell, the curve of dependence of E m on the logarithm of the ratio of potassium concentrations outside and inside the cell differs from the theoretical one. The established deviations in the experimental dependence of the MPP value and the concentration gradient of K + theoretically calculated using the Nernst equation can be explained by assuming that the MPP of excitable cells is determined not only by potassium, but also by sodium and chlorine equilibrium potentials. Arguing similarly to the previous one, we can write:

The values ​​of sodium and chlorine equilibrium potentials for spinal neurons (Table 1.1) are equal to +60 and -70 mV, respectively. The E Cl value is equal to the MPP value. This indicates the passive distribution of chlorine ions across the membrane in accordance with chemical and electrical gradients. For sodium ions, the chemical and electrical gradients are directed into 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 is calculated using the Goldmann 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 + vn, [ Na+ n [ Na + vn], [Cl - n ] and [Cl - ext ] - concentrations of K + , Na + and Cl outside (n) and inside (in) the cell.

Substituting the ion concentrations and the MPP value obtained in experimental studies into this equation, it can be shown that for the squid giant axon there should be the following ratio of permeability constants P to: P Na: P C1 = 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 chemical and electrical gradients will reduce the electronegativity of the cytoplasm, i.e. increase RMP (resting membrane potential).

When the concentration of potassium ions in the external solution increases above 15 mM, the MPP increases and the ratio of permeability constants changes towards a more significant excess of Pk over P Na and P C1. P k: P Na: P C1 = 1: 0.025: 0.4. Under such conditions, the MPP is determined almost exclusively by the gradient of potassium ions, so the experimental and theoretical dependences of the MPP value 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 the different permeability of the membrane for these ions. The main role in the generation of MPP is played by the diffusion of potassium ions from the cell into the external solution. Along with this, the MPP is also determined by the sodium and chlorine equilibrium potentials, and the contribution of each of them is determined by the relationships between the permeabilities of the cell plasma membrane for these ions.

All the factors listed above constitute the so-called ionic component RMP (resting membrane potential). Since neither potassium nor sodium equilibrium potentials are equal to the MPP. the cell must absorb Na + and lose K +. The constancy of the concentrations of these ions in the cell is maintained due to 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 when it functions, a net flow of positive charges arises from the cell into the extracellular fluid, causing an increase in the electronegativity of the cytoplasm in relation 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 hyperpolarization of the membrane, during which the MPP was significantly lower than the potassium equilibrium potential. This hyperpolarization was weakened by decreasing the temperature of the solution in which the cell was located and was suppressed by the specific Na + , K + -ATPase inhibitor ouabain.

From the above it follows that 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 external 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 irritation is applied to a nerve or muscle 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 one. This a short-term change in MPP that occurs during cell excitation, which on the oscilloscope screen has the form of a single peak, is called membrane action potential (MPD).

IVD in nervous and muscle tissues occurs when the absolute value of IVD (membrane depolarization) decreases to a certain critical value, called generation threshold MTD. In giant squid nerve fibers, the IVD is 60 mV. When the membrane is depolarized to -45 mV (IVD generation threshold), IVD occurs (Fig. 1.15).

Rice. 1.15 Action potential of the nerve fiber (A) and change in membrane conductivity for sodium and potassium ions (B).

During the occurrence of IVD in the squid axon, the membrane resistance decreases 25 times, from 1000 to 40 Ohm.cm 2, while the electrical capacitance does not change. This decrease in membrane resistance is due to an increase in the ionic permeability of the membrane upon excitation.

In its amplitude (100-120 mV), the MAP (Membrane Action Potential) is 20-50 mV higher than the MPP (Resting Membrane Potential). In other words, the inner side of the membrane for a short time becomes positively charged in relation to the outer one - “overshoot” or charge reversal.

From the Goldman equation it follows that only an increase in the permeability of the membrane to sodium ions can lead to such changes in the membrane potential. The value of E k is always less than the value of the MPP, so an increase in the membrane permeability for K + will increase the absolute value of the MPP. The sodium equilibrium potential has a plus sign, so a sharp increase in the permeability of the membrane to these cations leads to recharging of the membrane.

During IVD, the permeability of the membrane to sodium ions increases. Calculations have shown that if at rest the ratio of membrane permeability constants for K + , Na + and SG is 1: 0.04: 0.45, then at MTD - P k: P Na: P = 1: 20: 0.45 . Consequently, in a state of excitation, the nerve fiber membrane does not simply lose its selective ion permeability, but, on the contrary, from being selectively permeable to potassium ions at rest, it becomes selectively permeable to sodium ions. The increase in sodium permeability of the membrane is associated with the opening of voltage-gated sodium channels.

The mechanism that ensures the opening and closing of ion channels is called canal gate. It is customary to distinguish activation(m) and inactivation(h) gate. An ion channel can be in three main states: closed (m-gate closed; h-gate open), open (m- and h-gate open) and inactivated (m-gate open, h-gate closed) (Figure 1.16).

Rice. 1.16 Diagram of the positions 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, electric current, opens the m-gate of sodium channels (transition from state A to B) and ensures 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. A “regenerative” depolarization of the membrane occurs, as a result of which the potential of the inner side of the membrane tends to reach the sodium equilibrium potential.

The reason for the cessation of IVD growth (Membrane action potential) and repolarization of the cell membrane is:

A) Increased membrane depolarization, i.e. when E m -» E Na, resulting in a decrease in the electrochemical gradient for sodium ions, equal to E m -> E Na. In other words, the force “pushing” sodium into the cell decreases;

b) Depolarization of the membrane gives rise to the process of inactivation of sodium channels (closing of the h-gate; channel B state), which inhibits the growth of sodium permeability of the membrane and leads to its decrease;

V) 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.

Reducing the electrochemical potential for sodium ions and inactivating sodium channels reduces the magnitude of the incoming sodium current. At a certain point in time, the magnitude of the incoming sodium current is compared with the increased outgoing current - the growth of IVD stops. When the total outgoing current exceeds the incoming one, repolarization of the membrane begins, which also has a regenerative nature. The onset of repolarization 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 closed channels etc.

The IVD repolarization phase in some cells (for example, in cardiomyocytes and some smooth muscle cells) can slow down, forming plateau AP caused by 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 metabolicI forge. The first is due to the fact that 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. Trace hyperpolarization after rhythmic stimulation of cells is associated primarily with 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 MAP (Membrane Action Potential) is the accumulation of potassium ions at the outer surface of the membrane. The latter, as follows from the Goldman equation, leads to an increase in RMP (resting membrane potential).

Inactivation of sodium channels is associated important property nerve fiber calledrefractoriness .

During absolute refractory period the nerve fiber completely loses the ability to be excited by a stimulus of any strength.

Relative refractoriness, following the absolute one, is characterized by a higher threshold for the occurrence of MTD (Membrane action potential).

The idea of ​​membrane processes occurring during the excitation of a nerve fiber serves as the basis for understanding and the phenomenon accommodation. The basis of tissue accommodation at a low rate of increase in irritating current is an increase in the excitation threshold, which outstrips 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 increasing the potassium permeability of the membrane in the development of accommodation is that it leads to a drop in membrane resistance. Due to the decrease in resistance, the rate of membrane depolarization becomes even slower. The speed of accommodation is higher, the higher larger number sodium channels at the resting potential are in an inactivated state, the higher the rate of development of inactivation and the higher the potassium permeability of the membrane.

Conducting excitation

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The 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 stimulus is applied to a nerve fiber in the corresponding portion of the membrane, an action potential arises. The inner side of the membrane at a given point turns out to be positively charged relative to the neighboring one at rest. A current arises between points of the fiber having different potentials. (local current), directed from excited (sign (+) on the inside of the membrane) to non-excited (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 a critical level of membrane depolarization is reached in this area, an MAP (Membrane Action Potential) occurs. This process sequentially spreads throughout all areas of the nerve fiber.

In some cells (neurons, smooth muscles), the IVD is not of sodium nature, but is caused by the entry of Ca 2+ ions through voltage-dependent calcium channels. In cardiomyocytes, IVD generation is associated with incoming sodium and sodium-calcium currents.

Irritants

By nature, irritants are divided into:
physical (sound, light, temperature, vibration, osmotic pressure), electrical stimuli are of particular importance for biological systems;
chemical (ions, hormones, neurotransmitters, peptides, xenobiotics);
informational (voice commands, conventional signs, conditioned stimuli).

According to their biological significance, irritants are divided into:
adequate - stimuli for the perception of which the biological system has special adaptations;
inadequate - irritants that do not correspond to the natural specialization of the receptor cells on which they act.

A stimulus causes arousal only if it is strong enough. Excitation threshold - the minimum strength of the stimulus sufficient to cause excitation of the cell. The expression “threshold of excitation” has several synonyms: threshold of irritation, threshold strength of stimulus, threshold of strength.

Excitation as an active reaction of a cell to a stimulus

The cell's response to external influence (irritation) differs from the response of non-biological systems in the following features:
the energy for the cell reaction is not the energy of the stimulus, but the energy generated as a result of metabolism in the biological system itself;
the strength and form of the cell reaction is not determined by the strength and form of external influence (if the strength of the stimulus is above the threshold).

In some specialized cells, the reaction to the stimulus is particularly intense. This intense reaction is called arousal. Excitation is an active reaction of specialized (excitable) cells to an external influence, manifested in the fact that the cell begins to perform its specific functions.

An excitable cell can be in two discrete states:
state of rest (readiness to respond to external influences, perform internal work);
state of excitement (active performance of specific functions, performance of external work).

There are 3 types of excitable cells in the body:
nerve cells (excitation is manifested by the generation of an electrical impulse);
- muscle cells (excitation is manifested by contraction);
secretory cells (excitation is manifested by the release of biologically active substances into the intercellular space).

Excitability is the ability of a cell to move from a resting state to a state of excitation when exposed to a stimulus. Different cells have different excitability. The excitability of the same cell changes depending on its functional state.

Excitable cell at rest

The membrane of an excitable cell is polarized. This means that there is a constant potential difference between the inner and outer surface of the cell membrane, which is called membrane potential(MP). At rest, the MF value is –60…–90 mV (the inner side of the membrane is negatively charged relative to the outer). The MP value of a cell at rest is called resting potential(PP). Cell MP can be measured by placing one electrode inside and the other outside the cell (Fig. 1 A) .

A decrease in MP relative to its normal level (LP) is called depolarization, and an increase is called hyperpolarization. Repolarization is understood as the restoration of the initial level of MP after its change (see Fig. 1 B).

Electrical and physiological manifestations of arousal

Let us consider various manifestations of excitation using the example of irritating a cell with an electric current (Fig. 2).

Under the influence of weak (subthreshold) impulses electric current An electrotonic potential develops in the cell. Electrotonic potential(EP) – a shift in the cell membrane potential caused by the action of direct electric current . EP is a passive reaction of the cell to an electrical stimulus; the state of ion channels and ion transport do not change. EP does not manifest itself as a physiological reaction of the cell. Therefore, EP is not arousal.

Under the action of a stronger subthreshold current, a more prolonged shift of the MP occurs - a local response. Local response (LR) is an active reaction of the cell to an electrical stimulus, but the state of ion channels and ion transport changes slightly. LO does not manifest itself in a noticeable physiological reaction of the cell. LO is called local excitement , since this excitation does not spread across the membranes of excitable cells.

Under the influence of threshold and superthreshold current, the cell develops action potential(PD). AP is characterized by the fact that the cell MP value very quickly decreases to 0 (depolarization), and then the membrane potential acquires a positive value (+20...+30 mV), i.e., the inner side of the membrane is charged positively relative to the outer. Then the MP value quickly returns to its original level. Strong depolarization of the cell membrane during AP leads to the development of physiological manifestations of excitation (contraction, secretion, etc.). PD is called spreading excitement, because, having arisen in one section of the membrane, it quickly spreads in all directions.

The mechanism of AP development is almost the same for all excitable cells. The mechanism for coupling electrical and physiological manifestations of excitation is different for different types excitable cells (coupling of excitation and contraction, coupling of excitation and secretion).

The structure of the cell membrane of an excitable cell

Four types of ions are involved in the mechanisms of development of excitation: K+, Na+, Ca++, Cl – (Ca++ ions are involved in the processes of excitation of some cells, for example cardiomyocytes, and Cl – ions are important for the development of inhibition). The cell membrane, which is a lipid bilayer, is impermeable to these ions. In the membrane, there are 2 types of specialized integral protein systems that ensure the transport of ions across the cell membrane: ion pumps and ion channels.

Ion pumps and transmembrane ion gradients

Ion pumps (pumps)– integral proteins that provide active transport of ions against a concentration gradient. The energy for transport is the energy of ATP hydrolysis. There are Na+ / K+ pump (pumps out Na+ from the cell in exchange for K+), Ca++ pump (pumps out Ca++ from the cell), Cl– pump (pumps out Cl– from the cell).

As a result of the operation of ion pumps, transmembrane ion gradients are created and maintained:
concentration of Na+, Ca++, Cl – inside the cell is lower than outside (in the intercellular fluid);
the concentration of K+ inside the cell is higher than outside.

Ion channels

Ion channels are integral proteins that provide passive transport of ions along a concentration gradient. The energy for transport is the difference in ion concentration on both sides of the membrane (transmembrane ion gradient).

Non-selective channels
allow all types of ions to pass through, but the permeability for K+ ions is significantly higher than for other ions;
are always open.

Selective channels have the following properties:
only one type of ion passes through; for each type of ion there is its own type of channel;
can be in one of 3 states: closed, activated, inactivated.

The selective permeability of the selective channel is ensured selective filter , which is formed by a ring of negatively charged oxygen atoms, which is located at the narrowest point of the channel.

Changing the channel state is ensured by the operation gate mechanism, which is represented by two protein molecules. These protein molecules, the so-called activation gate and inactivation gate, by changing their conformation, can block the ion channel.

In the resting state, the activation gate is closed, the inactivation gate is open (the channel is closed) (Fig. 3). When a signal acts on the gate system, the activation gate opens and the transport of ions through the channel begins (the channel is activated). With significant depolarization of the cell membrane, the inactivation gate closes and ion transport stops (the channel is inactivated). When the MP level is restored, the channel returns to its original (closed) state.

Depending on the signal that causes the activation gate to open, selective ion channels are divided into:
• chemosensitive channels – the signal for the opening of the activation gate is a change in the conformation of the receptor protein associated with the channel as a result of the attachment of a ligand to it;
• potential sensitive channels – the signal to open the activation gate is a decrease in MP (depolarization) of the cell membrane to a certain level, which is called critical level of depolarization (KUD).

Mechanism of resting potential formation

The resting membrane potential is formed mainly due to the release of K+ from the cell through non-selective ion channels. The leakage of positively charged ions from the cell leads to the fact that the inner surface of the cell membrane becomes negatively charged relative to the outer one.

The membrane potential resulting from K+ leakage is called the “equilibrium potassium potential” ( Ek). It can be calculated using the Nernst equation

Where R– universal gas constant,
T– temperature (Kelvin),
F– Faraday number,
[K+]nar – concentration of K+ ions outside the cell,
[K+] ext – concentration of K+ ions inside the cell.

PP is usually very close to Ek, but not exactly equal to it. This difference is explained by the fact that the following contribute to the formation of PP:

entry of Na+ and Cl– into the cell through non-selective ion channels; in this case, the entry of Cl– into the cell additionally hyperpolarizes the membrane, and the entry of Na+ additionally depolarizes it; the contribution of these ions to the formation of PP is small, since the permeability of non-selective channels for Cl– and Na+ is 2.5 and 25 times lower than for K+;

direct electrogenic effect of the Na+ /K+ ion pump, which occurs if the ion pump operates asymmetrically (the number of K+ ions transferred into the cell is not equal to the number of Na+ ions carried out of the cell).

Mechanism of action potential development

There are several phases in the action potential (Fig. 4):

depolarization phase;
phase of rapid repolarization;
slow repolarization phase (negative trace potential);
hyperpolarization phase (positive trace potential).

Depolarization phase. The development of AP is possible only under the influence of stimuli that cause depolarization of the cell membrane. When the cell membrane is depolarized to a critical depolarization level (CDL), an avalanche-like opening of voltage-sensitive Na+ channels occurs. Positively charged Na+ ions enter the cell along a concentration gradient (sodium current), as a result of which the membrane potential very quickly decreases to 0 and then becomes positive. The phenomenon of changing the sign of the membrane potential is called reversion membrane charge.

Fast and slow repolarization phase. As a result of membrane depolarization, voltage-sensitive K+ channels open. Positively charged K+ ions leave the cell along a concentration gradient (potassium current), which leads to restoration of the membrane potential. At the beginning of the phase, the intensity of the potassium current is high and repolarization occurs quickly; towards the end of the phase, the intensity of the potassium current decreases and repolarization slows down.

Hyperpolarization phase develops due to residual potassium current and due to the direct electrogenic effect of the activated Na+ / K+ pump.

Overshoot– the period of time during which the membrane potential has a positive value.

Threshold potential – the difference between the resting membrane potential and the critical level of depolarization. The magnitude of the threshold potential determines the excitability of the cell - the higher the threshold potential, the less excitability of the cell.

Changes in cell excitability during the development of excitation

If we take the level of excitability of a cell in a state of physiological rest as the norm, then during the development of the excitation cycle, its fluctuations can be observed. Depending on the level of excitability, the following cell states are distinguished (see Fig. 4).

Supernormal excitability ( exaltation ) – a state of a cell in which its excitability is higher than normal. Supernormal excitability is observed during the initial depolarization and during the slow repolarization phase. The increase in cell excitability in these AP phases is due to a decrease in the threshold potential compared to the norm.

Absolute refractoriness - a state of a cell in which its excitability drops to zero. No stimulus, even the strongest, can cause additional stimulation of the cell. During the depolarization phase, the cell is non-excitable, since all its Na+ channels are already in an open state.

Relative refractoriness – a state in which the excitability of the cell is significantly lower than normal; Only very strong stimuli can excite the cell. During the repolarization phase, the channels return to a closed state and cell excitability is gradually restored.

Subnormal excitability is characterized by a slight decrease in cell excitability below the normal level. This decrease in excitability occurs due to an increase in the threshold potential during the hyperpolarization phase.

Introduction
Nervous system
regulates activities
the body thanks to
conducting information
(excitation) over the network
nerve cells.
The goal of neurophysiology is
this is to understand biological
mechanisms that lie
at the basis of
information on nervous
system.

Neurons carry information to large
distances using electrical signals,
which spread along the axon.
Used special type electrical
signals - nerve impulse or potential
actions.
The action potential is fundamental
carrier of information in the nervous system

Resting membrane potential of a neuron

The process of generating and distributing PD
occurs on the neuron membrane.
Cells that are capable of generating and conducting
nerve impulse have an excitable membrane.

Resting membrane potential of a neuron

If a neuron is not affected by a stimulus, then it
is at rest.
At rest, the outer side of the membrane
neuron is positively charged, and the internal one is
negative. This condition is called
resting membrane potential.
The resting membrane potential (RMP) is
potential difference across the neuron membrane, which
the neuron has a relative state
physiological rest.

Resting membrane potential of a neuron

Action potential is short-term
change in membrane potential at which
outer side of the membrane by one thousandth
second becomes negative, and internal -
positive.

Resting membrane potential of a neuron

1.
2.
3.
To understand how a neuron transmits information,
need to study:
how in a state of rest on the membrane
the neuron arises and is maintained by a membrane
resting potential;
how does membrane potential
changes briefly during generation
nerve impulse;
how does a nerve impulse travel
along the neuron membrane.

Resting membrane potential of a neuron

Mechanism of occurrence of MPP
Ion movement
MPP occurs as a result of the movement of ions
(charged particles) through ion channels
cell membranes.
Ions are atoms or molecules that have
positive (cations) or negative
(anions) charge.
For example, K+, Na+, Cl¯, Ca2+, etc.

Mechanism of occurrence of MPP

Movement of ions through
ion channels associated with
due to two factors:
1. diffusion
2. electric power
Diffusion is movement
ions from places with high
concentration in places with
low concentration.

Mechanism of occurrence of MPP

Terms
The concentration gradient is the difference
ion concentrations.
The concentration gradient force is the force
chemical nature that moves ions from
places with high concentration to places with low
concentration of a given ion.
Rule: the greater the concentration gradient, the
greater strength of the concentration gradient.

10. Mechanism of occurrence of MPP

Electric force (I) is
the force that moves
ions in an electric field.
Electric power
moves negative ones
ions (anions) to
positive charge
(anode), and positive ions
(cations) – to negative
charge (cathode).

11. Mechanism of occurrence of MPP

Movement of electric charges in electric
the field is called electric current.
The strength of the electric current is determined by two
factors:
1. electric potential
2. electrical conductivity

12. Mechanism of occurrence of MPP

Electric potential (V) is
a force that reflects differences in
charge between the cathode and anode.
The greater the difference in charge, the
the greater the electric potential, the
stronger ion current.
Electric potential is measured
in Volts (V).
Electrical conductivity is
relative ability
electric charges move in
electric field.
The higher the electric
conductivity, the stronger the ion current.

13. Mechanism of occurrence of MPP

Electrical resistance (R) – force,
preventing the movement of electrical charges.
Electrical resistance is measured in Ohms
(Ω) .
The relationship between electric potential,
resistance and current strength is described by the law
Oma.
I = V/R
The current is zero in two cases:
1. either the electric potential is zero,
2. or there is very high resistance.

14. Mechanism of occurrence of MPP

Movement of specific ions
through the membrane under the influence
electric force can be
only with simultaneous
meeting two conditions:
1. the membrane contains channels that
permeable to a given type of ions;
2. there is a potential difference across
both sides of the membrane.

15. Ionic mechanism of resting membrane potential

Membrane potential
(MP) is the difference
membrane potentials
neuron which neuron
has at the moment
time (Vm).
Membrane potential
neuron maybe
measured using
microelectrode,
placed in the cytoplasm
neuron and connected
to the voltmeter.

16. Ionic mechanism of resting membrane potential

At rest, the inner side of the membrane
is negatively charged, and the outer side is
positively.
Typical resting membrane potential (RMP)
neuron is approximately equal to - 65 mV.
Vm = -65 mV
To understand how it arises and
supported by WFP, should be considered
the distribution of certain ions within the neuron and
the external environment surrounding it.

17. Ionic mechanism of resting membrane potential

Equilibrium potential
Consider a hypothetical cell with
following conditions:
1. inside the cell the concentration of K+ cations and
A¯ anions is higher than in the external environment,
2. the cell membrane does not contain ionic
channels.
Under these conditions, despite the presence
differences in ion concentrations,
1. no ion current will be observed through
membrane;
2. the membrane potential will be equal
zero.

18. Ionic mechanism of resting membrane potential

The situation will change if
ion channels permeable to K+ ions, but
impermeable to A¯ anions.
K+ ions along the concentration gradient will begin
move from the cell to the extracellular environment.
Due to the negative ions A¯ on the internal
side of the membrane begins to accumulate
negative charge, and on the outside
the membrane begins to appear positive
charge.
Thus, on the membrane of the neuron begins
a potential difference appears.

19. Ionic mechanism of resting membrane potential

As the potential difference increases
electric force begins to increase,
which pushes K+ ions back into the cell (so
as positively charged K+ ions
are attracted to the negatively infected
layer on the inner side of the membrane).
When the membrane reaches a certain
membrane potential value
electric force trying to drive
K+ ions into the cell becomes equal
chemical force of the concentration gradient,
which tends to push K+ ions out of
cells.
A state of equilibrium occurs when
in which the force of electrical nature and the force
have the same chemical nature
meaning, but aimed at different sides, A
the movement of K+ ions stops.

20. Ionic mechanism of resting membrane potential

Ionic equilibrium potential is the difference
potentials on the membrane, at which the strength of the chemical and
electrical nature balance each other according to
relation to a given ion.
For example, the potassium equilibrium potential is
approximately – 80 mV.
Conclusion: the appearance of membrane potential in a neuron
occurs automatically if two conditions are met:
1. There is a difference in ion concentrations between external and
internal environment of the neuron;
2. there is selective permeability of the membrane
neuron for a given ion.

21. Ionic mechanism of resting membrane potential

22. Ionic mechanism of resting membrane potential

The difference in the concentrations of various ions in
real neuron
In a real neuron, different ions behave differently
distributed in intracellular and extracellular
environment.
Ions
Extracellular
concentration
Intracellular
concentration
Attitude
Equilibrium
potential
K+
5
100
1:20
-80 mV
Na+
150
15
10:1
62 mV
Ca2+
2
0,0002
10000:1
123 mV
Cl¯
150
13
11,5:1
-65 mV

23. Ionic mechanism of resting membrane potential

Each ion has its own
equilibrium potential.
Rule – the concentration of K+ ions is greater
inside the cell, and Na+ and Cl¯ ions
external environment.
Difference in concentrations of different ions
arises as a result of the work of several
ion pumps that are built into
neuron membrane.

24. Ionic mechanism of resting membrane potential

Two ion pumps are especially important
to understand how a neuron works:
1. sodium-potassium
2. calcium pump
Sodium-potassium pump
using ATP energy, pumps out
Na+ ions from the cell and pumped into
cell K+ ions against the gradient
concentrations of these ions.
In one cycle the pump pumps out
3
Na+ ion and 2 K+ ions.
It costs to operate this pump
more than 70% of all ATP,
located in the brain.

25. Ionic mechanism of resting membrane potential

The calcium pump pumps Ca2+ ions out of the neuron
against its concentration gradient.
1.
2.
In addition, there are additional mechanisms
which provide a decrease in ion concentration
Ca2+ in the cytoplasm of a neuron (0.00002 mM):
intracellular proteins that bind data
ions;
cellular organelles (in particular mitochondria and
endoplasmic reticulum), which deposit
(isolate) Ca2+ ions.

26. Ionic mechanism of resting membrane potential

Importance of Ion Pumps
Without ion pumps in a neuron I could not
concentration difference maintained
different ions, and, therefore, in
neuron could not exist
resting membrane potential, without which, in
in turn, the neuron would not be able to respond to
external influence and transmit
excitation.

27. Ionic mechanism of resting membrane potential

Relative membrane permeability for different ions
In a real neuron, the neuron membrane is permeable to not only one, but
for different ions.
However, the permeability of the membrane for different ions is different.
Let's consider several scenarios for Na+ and K+ ions:
1. If the membrane is permeable only to the K+ ion, then the membrane
the potential will be equal to the potassium equilibrium potential
(approximately -80 mV).
2. If the membrane is permeable only to the Na+ ion, then the membrane
the potential will be equal to the sodium equilibrium potential
(approximately 62 mV).
3. If the membrane has the same permeability for Na+ and K+ ions, then
membrane potential will be equal to the average value between
sodium and potassium equilibrium potential (approximately - 9 mV).

28. Ionic mechanism of resting membrane potential

4. If the permeability of the membrane is 40 times greater for K+ ions than
for Na+ ions, then the value of the final membrane potential
will again be between sodium and potassium equilibrium
potential, but at the same time closer to the potassium equilibrium
potential.
The last scenario is closest to the real situation
neuron in which the resting membrane potential is -65 mV.
In a real neuron at rest, the membrane has a high
permeability for K+ ions and relatively low for Na+ ions.

29. Ionic mechanism of resting membrane potential

Conclusion: high membrane permeability
neuron for K+ ions is the main
source of membrane potential
rest (RMP), with a relatively low
membrane permeability to other ions
(especially Na+ ions) also contributes
certain contribution to the final value
MPP of a neuron.

30. Ionic mechanism of resting membrane potential

Regulation of the concentration of K+ ions in the extracellular
environment
The membrane potential is very sensitive to
change in the concentration of K+ ions in the extracellular
environment. For example, if the concentration of K+ ions in
external environment will decrease by 10 times, then the membrane
the resting potential will change from -65 to -17 mV.
Sensitivity of membrane potential to
concentration of K+ ions led in evolution to
the emergence of mechanisms that finely regulate
the content of these ions in the extracellular environment:
1. blood-brain barrier
2. glial cells (astrocytes)

31. Ionic mechanism of resting membrane potential

The blood-brain barrier (BBB) ​​is
mechanism providing limited access
substances that enter through the walls of capillaries,
to neurons and glial cells inside the brain.
One of the functions of the BBB is to limit the flow from
blood K+ ions into the extracellular environment surrounding
neurons.

32. Ionic mechanism of resting membrane potential

Astrocytes provide
regulation of concentration
K+ ions using
potassium pumps and
potassium ion channels,
built into their membrane.
When extracellular
K+ ion concentration
increases, these ions begin
go inside astrocytes
through potassium ion
channels.

33. Ionic mechanism of resting membrane potential

Entry of K+ ions into the cytoplasm
astrocyte leads to increased
local intracellular
the concentrations of these ions,
who start
spread throughout the system
branched processes in
other parts of the glial cell.
Thus, astrocytes
have glial
buffer mechanism
which supports
concentration of K+ ions in
extracellular environment on
constant level.

34. Ionic mechanism of resting membrane potential

Conclusion
Mechanism of occurrence of MPP
1. The activity of the sodium-potassium pump ensures and
maintains a high concentration of K+ ions in
intracellular environment of the neuron.
2. The membrane of a neuron at rest has a high
permeability for K+ ions, since it has numerous
potassium channels.
3. Movement of K+ ions through the neuron membrane along their gradient
concentration leads to the appearance of a negative charge on
the inside of the membrane and the positive charge on
outside of the membrane.
4. The potential difference on the neuron membrane can
be considered as the charge of an electric battery, which
constantly maintained by ion pumps,
working on the basis of ATP energy.

Ion concentration inside and outside the cell

So, there are two facts that need to be taken into account in order to understand the mechanisms that maintain the resting membrane potential.

1 . The concentration of potassium ions in the cell is significantly higher than in the extracellular environment. 2 . The membrane at rest is selectively permeable to K +, and for Na + the permeability of the membrane at rest is insignificant. If we take the permeability for potassium to be 1, then the permeability for sodium at rest is only 0.04. Hence, there is a constant flow of K+ ions from the cytoplasm along a concentration gradient. The potassium current from the cytoplasm creates a relative deficiency of positive charges on the inner surface; the cell membrane is impenetrable for anions; as a result, the cell cytoplasm becomes negatively charged in relation to the environment surrounding the cell. This potential difference between the cell and the extracellular space, the polarization of the cell, is called the resting membrane potential (RMP).

The question arises: why does the flow of potassium ions not continue until the concentrations of the ion outside and inside the cell are balanced? It should be remembered that this is a charged particle, therefore, its movement also depends on the charge of the membrane. The intracellular negative charge, which is created due to the flow of potassium ions from the cell, prevents new potassium ions from leaving the cell. The flow of potassium ions stops when the action of the electric field compensates for the movement of the ion along the concentration gradient. Consequently, for a given difference in ion concentrations on the membrane, the so-called EQUILIBRIUM POTENTIAL for potassium is formed. This potential (Ek) is equal to RT/nF *ln /, (n is the valence of the ion.) or

Ek=61.5 log/

The membrane potential (MP) largely depends on the equilibrium potential of potassium; however, some sodium ions still penetrate into the resting cell, as well as chlorine ions. Thus, the negative charge that the cell membrane has depends on the equilibrium potentials of sodium, potassium and chlorine and is described by the Nernst equation. The presence of this resting membrane potential is extremely important, because it determines the cell's ability to excite - a specific response to a stimulus.

Cell excitation

IN excitement cells (transition from a resting to an active state) occurs when the permeability of ion channels for sodium and sometimes for calcium increases. The reason for the change in permeability can be a change in the membrane potential - electrically excitable channels are activated, and the interaction of membrane receptors with a biologically active substance - receptor - controlled channels, and mechanical action. In any case, for the development of arousal it is necessary initial depolarization - a slight decrease in the negative charge of the membrane, caused by the action of a stimulus. An irritant can be any change in the parameters of the external or internal environment of the body: light, temperature, chemicals (effects on taste and olfactory receptors), stretching, pressure. Sodium rushes into the cell, an ion current occurs and the membrane potential decreases - depolarization membranes.

Table 4

Change in membrane potential upon cell excitation.

Please note that sodium enters the cell along a concentration gradient and an electrical gradient: the sodium concentration in the cell is 10 times lower than in the extracellular environment and the charge relative to the extracellular is negative. Potassium channels are also activated at the same time, but sodium (fast) channels are activated and inactivated within 1 - 1.5 milliseconds, and potassium channels longer.

Changes in membrane potential are usually depicted graphically. The top figure shows the initial depolarization of the membrane - the change in potential in response to the action of a stimulus. For each excitable cell there is a special level of membrane potential, upon reaching which the properties of sodium channels sharply change. This potential is called critical level of depolarization (KUD). When the membrane potential changes to KUD, fast, voltage-dependent sodium channels open, and a flow of sodium ions rushes into the cell. When positively charged ions enter the cell, the positive charge increases in the cytoplasm. As a result of this, the transmembrane potential difference decreases, the MP value decreases to 0, and then, as sodium continues to enter the cell, the membrane is recharged and the charge is reversed (overshoot) - now the surface becomes electronegative with respect to the cytoplasm - the membrane is completely DEPOLARIZED - middle picture. No further change in charge occurs because sodium channels are inactivated– more sodium cannot enter the cell, although the concentration gradient changes very slightly. If the stimulus has such a force that it depolarizes the membrane to CUD, this stimulus is called threshold; it causes excitation of the cell. The potential reversal point is a sign that the entire range of stimuli of any modality has been translated into the language of the nervous system - excitation impulses. Impulses or excitation potentials are called action potentials. Action potential (AP) is a rapid change in membrane potential in response to a stimulus of threshold strength. AP has standard amplitude and time parameters that do not depend on the strength of the stimulus - the “ALL OR NOTHING” rule. The next stage is the restoration of the resting membrane potential -(bottom figure) is mainly due to active ion transport. The most important process of active transport is the work of the Na/K pump, which pumps sodium ions out of the cell while simultaneously pumping potassium ions into the cell. The restoration of the membrane potential occurs due to the flow of potassium ions from the cell - potassium channels are activated and allow potassium ions to pass through until the equilibrium potassium potential is reached. This process is important because until the MPP is restored, the cell is not able to perceive a new impulse of excitation.

HYPERPOLARIZATION is a short-term increase in MP after its restoration, which is caused by an increase in membrane permeability for potassium and chlorine ions. Hyperpolarization occurs only after AP and is not typical for all cells. Let us once again try to graphically represent the phases of the action potential and the ionic processes underlying changes in membrane potential (Fig. 9). On the abscissa axis we plot the values ​​of the membrane potential in millivolts, on the ordinate axis we plot time in milliseconds.

1. Depolarization of the membrane to CUD - any sodium channels can open, sometimes calcium, both fast and slow, and voltage-gated and receptor-gated. It depends on the type of stimulus and the type of cells

2. Rapid entry of sodium into the cell - fast, voltage-dependent sodium channels open, and depolarization reaches the potential reversal point - the membrane is recharged, the sign of the charge changes to positive.

3. Restoration of the potassium concentration gradient - pump operation. Potassium channels are activated, potassium moves from the cell to the extracellular environment - repolarization, restoration of MPP begins

4. Trace depolarization, or negative trace potential - the membrane is still depolarized relative to the MPP.

5. Trace hyperpolarization. Potassium channels remain open and the additional potassium current hyperpolarizes the membrane. After this, the cell returns to its original level of MPP. The duration of PD is for different cells from 1 to 3-4 ms.

Figure 9 Action potential phases

Pay attention to the three potential values, important and constant for each cell, its electrical characteristics.

1. MPP - electronegativity of the cell membrane at rest, providing the ability to excite - excitability. In the figure, MPP = -90 mV.

2. CUD - critical level of depolarization (or threshold for generation of membrane action potential) - this is the value of the membrane potential, upon reaching which they open fast, voltage-dependent sodium channels and the membrane is recharged due to the entry of positive sodium ions into the cell. The higher the electronegativity of the membrane, the more difficult it is to depolarize it to CUD, the less excitable such a cell.

3. Potential reversal point (overshoot) - this value positive membrane potential, at which positively charged ions no longer penetrate the cell - short-term equilibrium sodium potential. In the figure + 30 mV. The total change in membrane potential from –90 to +30 will be 120 mV for a given cell, this value is the action potential. If this potential arises in a neuron, it will spread along the nerve fiber; if in muscle cells, it will spread along the muscle fiber membrane and lead to contraction; in glandular cells, to secretion, to cell action. This is the specific response of the cell to the action of the stimulus, excitation.

When exposed to a stimulus subliminal strength incomplete depolarization occurs - LOCAL RESPONSE (LO). Incomplete or partial depolarization is a change in membrane charge that does not reach the critical depolarization level (CLD).

• managed. By control mechanism: electrically, chemically and mechanically controlled;
• uncontrollable. They do not have a gate mechanism and are always open, ions flow constantly, but slowly.

Resting potential- this is the difference in electrical potential between the external and internal environment of the cell.

The mechanism of formation of resting potentials. The immediate cause of the resting potential is the unequal concentration of anions and cations inside and outside the cell. Firstly, this arrangement of ions is justified by the difference in permeability. Secondly, significantly more potassium ions leave the cell than sodium.

Action potential- this is the excitation of the cell, the rapid fluctuation of the membrane potential due to the diffusion of ions into and out of the cell.

When a stimulus acts on cells of excitable tissue, sodium channels are first very quickly activated and inactivated, then potassium channels are activated and inactivated with some delay.

As a result, ions quickly diffuse into or out of the cell along an electrochemical gradient. This is excitement. Based on the change in the magnitude and sign of the cell charge, three phases are distinguished:

• 1st phase - depolarization. Reducing the cell charge to zero. Sodium moves towards the cell according to a concentration and electrical gradient. Motion condition: sodium channel gate open;
• 2nd phase - inversion. Reversing the charge sign. Inversion involves two parts: ascending and descending.

The ascending part. Sodium continues to move into the cell according to the concentration gradient, but against the electrical gradient (it interferes).

Descending part. Potassium begins to leave the cell according to a concentration and electrical gradient. The gate of the potassium channel is open;

• 3rd phase - repolarization. Potassium continues to leave the cell according to the concentration gradient, but contrary to the electrical gradient.

Excitability criteria

With the development of an action potential, a change in tissue excitability occurs. This change occurs in phases. The state of the initial polarization of the membrane typically reflects the resting membrane potential, which corresponds to the initial state of excitability and, therefore, the initial state of the excitable cell. This is a normal level of excitability. The pre-spike period is the period of the very beginning of the action potential. Tissue excitability is slightly increased. This phase of excitability is primary exaltation (primary supernormal excitability). During the development of the prespike, the membrane potential approaches the critical level of depolarization, and to achieve this level, the stimulus strength may be less than the threshold.

During the period of development of the spike (peak potential), there is an avalanche-like flow of sodium ions into the cell, as a result of which the membrane is recharged, and it loses the ability to respond with excitation to stimuli of above-threshold strength. This phase of excitability is called absolute refractoriness, i.e. absolute inexcitability, which lasts until the end of membrane recharging. Absolute membrane refractoriness occurs due to the fact that sodium channels completely open and then inactivate.

After the end of the recharging phase, its excitability is gradually restored to its original level - this is a phase of relative refractoriness, i.e. relative inexcitability. It continues until the membrane charge is restored to a value corresponding to the critical level of depolarization. Since during this period the resting membrane potential has not yet been restored, the excitability of the tissue is reduced, and new excitation can arise only under the action of a superthreshold stimulus. The decrease in excitability in the relative refractory phase is associated with partial inactivation of sodium channels and activation of potassium channels.

The next period corresponds to an increased level of excitability: the phase of secondary exaltation or secondary supernormal excitability. Since the membrane potential in this phase is closer to the critical level of depolarization, compared to the resting state of the initial polarization, the stimulation threshold is reduced, i.e. cell excitability is increased. During this phase, new excitation can arise from the action of stimuli of subthreshold strength. Sodium channels are not completely inactivated during this phase. The membrane potential increases—a state of membrane hyperpolarization occurs. Moving away from the critical level of depolarization, the threshold of stimulation slightly increases, and new excitation can arise only under the influence of stimuli of a supra-threshold value.

The mechanism of occurrence of the resting membrane potential

Each cell at rest is characterized by the presence of a transmembrane potential difference (resting potential). Typically, the charge difference between the inner and outer surfaces of the membranes is -80 to -100 mV and can be measured using external and intracellular microelectrodes (Fig. 1).

The potential difference between the outer and inner sides of the cell membrane in its resting state is called membrane potential (resting potential).

The creation of the resting potential is ensured by two main processes - the uneven distribution of inorganic ions between the intra- and extracellular spaces and the unequal permeability of the cell membrane to them. Analysis chemical composition extra- and intracellular fluid indicates an extremely uneven distribution of ions (Table 1).

At rest, there are many anions of organic acids and K+ ions inside the cell, the concentration of which is 30 times higher than outside; On the contrary, there are 10 times more Na+ ions outside the cell than inside; CI- is also larger on the outside.

At rest, the membrane of nerve cells is most permeable to K+, less permeable to CI- and very little permeable to Na+. The permeability of the nerve fiber membrane to Na+ at rest is 100 times less than for K+. For many anions of organic acids, the membrane at rest is completely impermeable.

Rice. 1. Measuring the resting potential of a muscle fiber (A) using an intracellular microelectrode: M - microelectrode; I - indifferent electrode. The beam on the oscilloscope screen (B) shows that before the membrane was pierced by the microelectrode, the potential difference between M and I was equal to zero. At the moment of puncture (shown by an arrow), a potential difference was detected, indicating that the inner side of the membrane is negatively charged relative to its outer surface (according to B.I. Khodorov)

Table. Intra- and extracellular concentrations of ions in the muscle cell of a warm-blooded animal, mmol/l (according to J. Dudel)

	Intracellular concentration	Extracellular concentration
A- (anions of organic compounds)

Due to the concentration gradient, K+ reaches the outer surface of the cell, carrying out its positive charge. High molecular weight anions cannot follow K+ because the membrane is impermeable to them. The Na+ ion also cannot replace the lost potassium ions, because the permeability of the membrane for it is much less. CI- along the concentration gradient can only move inside the cell, thereby increasing the negative charge of the inner surface of the membrane. As a result of this movement of ions, polarization of the membrane occurs when its outer surface is charged positively and the inner surface is charged negatively.

The electric field that is created on the membrane actively interferes with the distribution of ions between the internal and external contents of the cell. As the positive charge on the outer surface of the cell increases, it becomes increasingly difficult for the K+ ion, which is positively charged, to move from inside to outside. It seems to be moving uphill. The greater the positive charge on the outer surface, the less K+ ions can reach the cell surface. At a certain potential on the membrane, the number of K+ ions crossing the membrane in both directions turns out to be equal, i.e. The potassium concentration gradient is balanced by the potential present across the membrane. The potential at which the diffusion flux of ions becomes equal to the flux of like ions moving in the opposite direction is called the equilibrium potential for a given ion. For K+ ions, the equilibrium potential is -90 mV. In myelinated nerve fibers, the value of the equilibrium potential for CI- ions is close to the value of the resting membrane potential (-70 mV). Therefore, despite the fact that the concentration of CI- ions outside the fiber is greater than inside it, their one-way current is not observed in accordance with the concentration gradient. In this case, the concentration difference is balanced by the potential present on the membrane.

The Na+ ion along the concentration gradient should enter into the cell (its equilibrium potential is +60 mV), and the presence of a negative charge inside the cell should not interfere with this flow. In this case, the incoming Na+ would neutralize the negative charges inside the cell. However, this does not actually happen, since the membrane at rest is poorly permeable to Na+.

The most important mechanism that maintains a low intracellular concentration of Na+ ions and a high concentration of K+ ions is the sodium-potassium pump (active transport). It is known that in the cell membrane there is a system of carriers, each of which is bound by the stirrup Na+ ions located inside the cell and carries them out. From the outside, the carrier binds to two K+ ions located outside the cell, which are transferred into the cytoplasm. The energy supply for the operation of transporter systems is provided by ATP. The operation of a pump using such a system leads to the following results:

• a high concentration of K+ ions is maintained inside the cell, which ensures a constant value of the resting potential. Due to the fact that during one cycle of ion exchange one more positive ion is removed from the cell than is introduced, active transport plays a role in creating the resting potential. In this case, they talk about an electrogenic pump, since it itself creates a small but constant current of positive charges from the cell, and therefore makes a direct contribution to the formation of a negative potential inside it. However, the magnitude of the contribution of the electrogenic pump to general meaning the resting potential is usually small and amounts to several millivolts;
• a low concentration of Na + ions is maintained inside the cell, which, on the one hand, ensures the operation of the action potential generation mechanism, and on the other hand, ensures the preservation of normal osmolarity and cell volume;
• maintaining a stable concentration gradient of Na +, the sodium-potassium pump promotes the coupled K +, Na + -transport of amino acids and sugars across the cell membrane.

Thus, the occurrence of a transmembrane potential difference (resting potential) is due to the high conductivity of the cell membrane at rest for K +, CI- ions, ionic asymmetry of the concentrations of K + ions and CI- ions, the work of active transport systems (Na + / K + -ATPase), which create and maintain ionic asymmetry.

Nerve fiber action potential, nerve impulse

Action potential - This is a short-term fluctuation in the potential difference of the membrane of an excitable cell, accompanied by a change in its charge sign.

The action potential is fundamental specific sign excitement. Its registration indicates that the cell or its structures responded to the impact with excitation. However, as already noted, PD in some cells can occur spontaneously (spontaneously). Such cells are found in the pacemakers of the heart, the walls of blood vessels, and the nervous system. AP is used as a carrier of information, transmitting it in the form of electrical signals (electrical signaling) along afferent and efferent nerve fibers, the conduction system of the heart, and also to initiate contraction of muscle cells.

Let us consider the reasons and mechanism of AP generation in the afferent nerve fibers that form the primary sensory receptors. The immediate cause of the occurrence (generation) of APs in them is the receptor potential.

If we measure the potential difference on the membrane of the node of Ranvier closest to the nerve ending, then in the intervals between exposures to the Pacinian corpuscle capsule it remains unchanged (70 mV), and during exposure it depolarizes almost simultaneously with the depolarization of the receptor membrane of the nerve ending.

With an increase in the pressure force on the Pacinian body, causing an increase in the receptor potential to 10 mV, a rapid oscillation of the membrane potential is usually recorded at the nearest node of Ranvier, accompanied by recharging of the membrane - the action potential (AP), or nerve impulse (Fig. 2). If the force of pressure on the body increases even more, the amplitude of the receptor potential increases and a number of action potentials with a certain frequency are generated in the nerve ending.

Rice. 2. Schematic representation of the mechanism for converting the receptor potential into an action potential (nerve impulse) and propagating the impulse along the nerve fiber

The essence of the mechanism of AP generation is that the receptor potential causes the appearance of local circular currents between the depolarized receptor membrane of the unmyelinated part of the nerve ending and the membrane of the first node of Ranvier. These currents, carried by Na+, K+, CI- and other mineral ions, “flow” not only along, but also across the membrane of the nerve fiber in the area of ​​the node of Ranvier. In the membrane of the nodes of Ranvier, in contrast to the receptor membrane of the nerve ending itself, there is a high density of ion voltage-dependent sodium and potassium channels.

When the depolarization value of about 10 mV is reached at the Ranvier interception membrane, fast voltage-dependent sodium channels open and through them a flow of Na+ ions rushes into the axoplasm along the electrochemical gradient. It causes rapid depolarization and recharging of the membrane at the node of Ranvier. However, simultaneously with the opening of fast voltage-gated sodium channels in the membrane of the node of Ranvier, slow voltage-gated potassium channels open and K+ ions begin to leave the axoillasma. Their output lags behind the entry of Na+ ions. Thus, Na+ ions entering the axoplasm at high speed quickly depolarize and recharge the membrane for a short time (0.3-0.5 ms), and K+ ions exiting restore the original distribution of charges on the membrane (repolarize the membrane). As a result, during a mechanical impact on the Pacinian corpuscle with a force equal to or exceeding the threshold, a short-term potential oscillation is observed on the membrane of the nearest node of Ranvier in the form of rapid depolarization and repolarization of the membrane, i.e. PD (nerve impulse) is generated.

Since the direct cause of AP generation is the receptor potential, in this case it is also called the generator potential. The number of nerve impulses of equal amplitude and duration generated per unit time is proportional to the amplitude of the receptor potential, and, consequently, to the force of pressure on the receptor. The process of converting information about the force of influence contained in the amplitude of the receptor potential into a number of discrete nerve impulses is called discrete information coding.

The ionic mechanisms and time dynamics of AP generation processes were studied in more detail under experimental conditions under artificial exposure of the nerve fiber to electric current of varying strength and duration.

The nature of the nerve fiber action potential (nerve impulse)

The nerve fiber membrane at the point of localization of the stimulating electrode responds to the influence of a very weak current that has not yet reached the threshold value. This response is called local, and the oscillation of the potential difference on the membrane is called local potential.

A local response on the membrane of an excitable cell can precede the occurrence of an action potential or occur as an independent process. It represents a short-term fluctuation (depolarization and repolarization) of the resting potential, not accompanied by membrane recharging. Depolarization of the membrane during the development of local potential is due to the advanced entry of Na+ ions into the axoplasm, and repolarization is due to the delayed exit of K+ ions from the axoplasm.

If the membrane is exposed to an electric current of increasing strength, then at this value, called the threshold, the depolarization of the membrane can reach a critical level - Ec, at which the opening of fast voltage-dependent sodium channels occurs. As a result, an avalanche-like increase in the flow of Na+ ions into the cell occurs through them. The induced depolarization process becomes self-accelerating, and the local potential develops into an action potential.

It has already been mentioned that a characteristic sign of PD is a short-term inversion (change) of the sign of the charge on the membrane. Outside, it becomes negatively charged for a short time (0.3-2 ms), and positively charged inside. The magnitude of the inversion can be up to 30 mV, and the magnitude of the entire action potential is 60-130 mV (Fig. 3).

Table. Comparative characteristics of local potential and action potential

Characteristic	Local potential	Action potential
Conductivity	Spreads locally, 1-2 mm with attenuation (decrement)	Spreads without attenuation over long distances along the entire length of the nerve fiber
Law of "force"	Submits	Doesn't obey
All or nothing law	Doesn't obey	Submits
Summation phenomenon	Summarizes, increases with repeated frequent subthreshold stimulation	Does not add up
Amplitude value
Excitability	Increases	Decreases to the point of complete inexcitability (refractoriness)
Stimulus magnitude	Subliminal	Threshold and superthreshold

The action potential, depending on the nature of the change in charges on the inner surface of the membrane, is divided into phases of depolarization, repolarization and hyperpolarization of the membrane. Depolarization call the entire ascending part of the PD, in which areas corresponding to the local potential are identified (from the level E 0 before E k), rapid depolarization (from the level E k to level 0 mV), inversions charge sign (from 0 mV to the peak value or the beginning of repolarization). Repolarization called the descending part of the AP, which reflects the process of restoration of the original polarization of the membrane. At first, repolarization occurs quickly, but as it approaches the level E 0, the speed can slow down and this section is called trace negativity(or trace negative potential). In some cells, following repolarization, hyperpolarization develops (an increase in membrane polarization). They call her trace positive potential.

The initial high-amplitude fast-flowing part of the AP is also called peak, or spike. It includes phases of depolarization and rapid repolarization.

In the mechanism of development of PD vital role belongs to voltage-gated ion channels and a non-simultaneous increase in the permeability of the cell membrane for Na+ and K+ ions. Thus, when an electric current acts on a cell, it causes depolarization of the membrane and, when the membrane charge decreases to a critical level (Ec), voltage-gated sodium channels open. As already mentioned, these channels are formed by protein molecules embedded in the membrane, inside which there is a pore and two gate mechanisms. One of the gate mechanisms, activation, ensures (with the participation of segment 4) the opening (activation) of the channel during membrane depolarization, and the second (with the participation of the intracellular loop between the 3rd and 4th domains) ensures its inactivation, which develops when the membrane is recharged (Fig. 4). Since both of these mechanisms rapidly change the position of the channel gate, voltage-gated sodium channels are fast ion channels. This circumstance is of decisive importance for the generation of AP in excitable tissues and for its conduction along the membranes of nerve and muscle fibers.

Rice. 3. Action potential, its phases and ionic currents (a, o). Description in the text

Rice. 4. The position of the gate and the state of activity of voltage-gated sodium and potassium channels during various levels membrane polarization

In order for the voltage-gated sodium channel to allow Na+ ions to pass into the cell, only the activation gate must be opened, since the inactivation gate is open under resting conditions. This is what happens when membrane depolarization reaches a level E k(Fig. 3, 4).

The opening of the activation gate of sodium channels leads to an avalanche-like entry of sodium into the cell, driven by the forces of its electrochemical gradient. Since Na+ ions carry a positive charge, they neutralize excess negative charges on the inner surface of the membrane, reduce the potential difference across the membrane and depolarize it. Soon, Na+ ions impart an excess of positive charges to the inner surface of the membrane, which is accompanied by an inversion (change) of the charge sign from negative to positive.

However, sodium channels remain open for only about 0.5 ms and after this period of time from the moment of onset

AP closes the inactivation gate, sodium channels become inactivated and impermeable to Na+ ions, the entry of which into the cell is sharply limited.

From the moment of membrane depolarization to the level E k activation of potassium channels and opening of their gates for K+ ions are also observed. K+ ions, under the influence of concentration gradient forces, leave the cell, removing positive charges from it. However, the gate mechanism of potassium channels is slow-functioning and the rate of exit of positive charges with K+ ions from the cell to the outside lags behind the entry of Na+ ions. The flow of K+ ions, removing excess positive charges from the cell, causes the restoration of the original distribution of charges on the membrane or its repolarization, and on the inner side, a moment after recharging, the negative charge is restored.

The occurrence of AP on excitable membranes and the subsequent restoration of the original resting potential on the membrane is possible because the dynamics of the entry into and exit of the positive charges of Na+ and K+ ions into the cell and exit from the cell are different. The entrance of the Na+ ion is ahead of the exit of the K+ ion. If these processes were in equilibrium, then the potential difference across the membrane would not change. Development of the ability to excite and generate PD by excitable muscle and nerve cells was due to the formation of two types of different-speed ion channels in their membrane - fast sodium and slow potassium.

To generate a single AP, a relatively small amount of energy is required to enter the cell. large number Na+ ions, which does not disrupt its distribution outside and inside the cell. If a large number of APs are generated, the distribution of ions on both sides of the cell membrane could be disrupted. However, in normal conditions this is prevented by the operation of the Na+, K+ pump.

Under natural conditions, in neurons of the central nervous system, the action potential primarily arises in the region of the axon hillock, in afferent neurons - in the node of Ranvier of the nerve ending closest to the sensory receptor, i.e. in those parts of the membrane where there are fast selective voltage-gated sodium channels and slow potassium channels. In other types of cells (for example, pacemaker, smooth myocytes), not only sodium and potassium channels, but also calcium channels play a role in the occurrence of AP.

The mechanisms of perception and transformation of signals into action potentials in secondary sensory receptors differ from the mechanisms discussed for primary sensory receptors. In these receptors, the perception of signals is carried out by specialized neurosensory (photoreceptor, olfactory) or sensoroepithelial (taste, auditory, vestibular) cells. Each of these sensitive cells has its own special mechanism for perceiving signals. However, in all cells the energy of the perceived signal (stimulus) is converted into an oscillation of the potential difference of the plasma membrane, i.e. into receptor potential.

Thus, the key point in the mechanisms by which sensory cells convert perceived signals into receptor potential is a change in the permeability of ion channels in response to the stimulus. The opening of Na +, Ca 2+, K + -ion channels during signal perception and transformation is achieved in these cells with the participation of G-proteins, second intracellular messengers, binding to ligands, and phosphorylation of ion channels. As a rule, the receptor potential that arises in sensory cells causes the release of a neurotransmitter from them into the synaptic cleft, which ensures the transmission of a signal to the postsynaptic membrane of the afferent nerve ending and the generation of a nerve impulse on its membrane. These processes are described in detail in the chapter on sensory systems.

The action potential can be characterized by amplitude and duration, which for the same nerve fiber remain the same as the action propagates along the fiber. Therefore, the action potential is called a discrete potential.

There is a certain connection between the nature of the impact on sensory receptors and the number of APs that arise in the afferent nerve fiber in response to the impact. It lies in the fact that with greater strength or duration of exposure, a greater number of nerve impulses are formed in the nerve fiber, i.e. with increasing impact in nervous system impulses of higher frequency will be sent from the receptor. The processes of converting information about the nature of the effect into frequency and other parameters of nerve impulses transmitted to the central nervous system are called discrete information coding.