Физиология и этология животных теоретический курс (возбудимые ткани) = Physiology and ethology of Animals theoretical course (excitable tissues). Учеб

tion leading to specific activity of cells is the only form of response to stimulation.

3) Inhibition is the process of suppressing the manifestations of the vital activity of excitable tissues, which, along with excitation, ensures the adaptation of living tissue to the environment of existence. However, by its nature, this is an active process (what is different from fatigue), the result of which is the restriction, delay of excitation.

2.2.Excitation laws

1)The law of force.

Excitable tissue responds to the action of a stimulus of a certain strength.

The measure of excitability of tissues is the excitability threshold (stimulation threshold) - this is the minimum strength of the stimulus, which is capable of causing the excitation process.

The strength of irritation can be:

Subthreshold - does not cause visible changes in tissues (subthreshold stimulus).

Threshold - this is the minimum force that causes excitation (threshold stimulus).

Superthreshold - with increasing strength of stimulation (superthreshold stimulus), it is subdivided:

submaximal - causes an increase in tissue response;

maximum - causes the maximum response;

supermaximal - causes a decrease in the response.

Thus, for the transition of an excitable tissue from a state of rest to an excitation state, it is necessary that the strength of the acting stimulus reaches a threshold value.

The magnitude of the threshold characterizes the comparative excitability of different tissues. The lower the excitation threshold (stimulus strength), the higher the excitability. The threshold of ex-

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citation of the nerve is lower than the threshold of excitation of the muscle and especially of the gland. The functional state of the tissue (work, fatigue, metabolic rate, etc.) also affect the threshold value.

2) The law of time.

Excitable tissue responds to the action of the stimulus of the threshold force and higher only if the stimulus acts for a certain time.

The shortest time during which the stimulus of the threshold force should act to induce excitation is called useful time.

There is a definite relationship between the strength and duration of the action of the stimulus. The stronger the stimulus, the shorter will be the time of its action, which is necessary for the onset of excitation.

Chronaxy is determined to assess the excitability of the tissue. Chronaxy is the shortest time necessary for the development of the response of an excitable tissue when an electric current is

applied to it, whose strength is equal to two threshold forces (twice the rheobase).

The rheobase is the threshold force of the stimulus-the electric current. Chronaxy is measured in milliseconds (ms) by a special device - chronaximeter.

Useful time and chronaxy are a measure of tissue excitability. The less they are, the higher the excitability of the tissue, and vice versa. Chronaxy is a variable quantity and depends on the structure and condition of the tissue and the whole organism. Therefore, the measurement of chronaxy is widely practiced to assess the functional state of the tissue. For example, in motor nerves the magnitude of chronaxy is less than in skeletal muscles (in a horse 0.09-0.2 ms and 0.2-0.4 ms, respectively); flexors less than extensors; nerves of the autonomic nervous system have a very high chronaxy (5 ms).

3) The law of the gradient.

For the onset of excitation, the rapidity of the increase in the strength of the stimulus, which is called the gradient of stimula-

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tion, also has significance. The law of the gradient is applicable to the action of any stimulus. If it is very slow to increase the current that affects the tissue, then excitation does not occur. This phenomenon is explained by the fact that during this time the tissues have time to develop changes that significantly increase the threshold of excitability and prevent the onset of excitation. Adaptation of tissue to a slowly increasing force of irritation is called accommodation. The indicator of accommodation is the minimum rate of increase in the strength of the stimulus, in which it is still capable of provoking a tissue response. The rate of accommodation varies in different tissues, for example, motor nerves are higher than sensory nerves, and very small in the heart muscle and smooth muscles of the stomach, intestines and ureters.

4) The law of action of direct current or the polar law of the action of the stimulus (Pfluger’s law).

Irritation of the nerve with a constant electric current causes excitability and conductivity at the points of application of electrodes to the nerve, which depends on the polarity (current direction) and the current strength. Under the action of a direct current on the tissue, tissue excitation occurs at the time of closure of the chain only under the cathode (hyperpolarization), while in the anode region excitability decreases, and at the moment of opening the chain, excitation occurs only under the anode (depolarization).

The main component of the excitatory process is the vibrations of the membrane potential of the cells, i.e. bioelectrical processes. Excitation in the nervous and muscle tissues is carried out electrically - by means of the action potential. Having arisen in one cell or section, the action potential becomes an irritant for neighboring cells or patches. The presence of an action potential is the most accurate indicator of the excitation that occurs in cells, tissues and organs.

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2.2. Bioelectric phenomena in living tissues, the theory of the appearance of biopotentials

The existence of a true “animal electricity” as a manifestation of the processes of the vital activity of tissues was established by the Italian researcher L. Galvani, who published “A Treatise on the Power of Electricity in Muscle Motion” in 1791. In experiments on the neuromuscular frog preparation, the scientist discovered that when the nerve and muscle of a chain of two metal conductors are shorted, the muscles contract. This fact was interpreted as a manifestation of the discharge of electricity, “pre-existent” in living tissue.

In the XIX century by the efforts of J. Bernstein, K. Mateuchchi, E. Dubois-Reymond, L. Herman, I.M. Sechenov, V.Ya. Danilevsky et al. the following initial positions of electrophysiology were formulated:

-between the internal contents of the cell (fiber) and the external solution at rest there is a stationary potential difference - the quiescent current;

-when there is irritation or damage of the tissue, certain fluctuations of the quiescent current occur, action currents occur;

-the action currents can have a single-phase nature (when the electrodes are connected to the intact and damaged parts of the nerve or muscle) or biphasic (when both discharge electrodes are applied to undamaged areas at the time of nerve or muscle excitation);

-the currents of action are amenable to registration, they can serve as a source of irritation to another excitable biological object.

By the end of the 19th century, it became obvious that electrical potentials (action currents as transformed resting currents) appear in virtually all functioning organs - the heart, kidneys, nerves, muscles, the retina of the eye, different parts of the brain.

In the XX century in connection with the successes of neurophysiology, biophysics and electronic instrumentation, perfect

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models of galvanometers, oscillographs, converters, amplifiers, writing recorders, microelectrodes, electronic stimulators were developed. This allowed us to study and understand in detail the biochemical and molecular nature of biopotentials and the mechanisms of their generation, as well as to create a number of universal instruments for the objective evaluation and recording of biopotentials, and to develop methods for using electrophysiological indicators in the clinical and scientific research.

In all excitable cells, there is an electrical potential between the inner side of the plasma membrane and the cell surface. This membrane resting potential has a certain directionality (the inner side is charged negatively with respect to the outside) and the value characteristic for each kind of cells. In homothermous animals it is: in fibers of skeletal muscles - 90 mV, in cells of myocardium - 80 mV, in nerve cells and fibers - 60-70 mV, in secretory glandular cells - 30-40 mV, in smooth muscle cells - 30-70 mV. In other living cells, there is also a resting potential, but its value is much smaller (for example, in erythrocytes - 7-10 mV).

According to the membrane-ion theory, the rest potential is due to two factors:

1)the asymmetric distribution of ions between the internal contents of the cell and the extracellular fluid;

2)the selective permeability of the membrane, which is due to the presence of pores in it, or “channels” (up to 500 per 10-6 mm2 surface), intended for the passage of different ions.

The main cation of extracellular fluid is sodium, its concentration outside the cell is 5-15 times higher than inside the cell (fiber). The main cation inside the cell is potassium, its concentration here is 20-40 times higher than in the extracellular fluid. The main anions of the extracellular fluid are chloride and bicarbonate; Intracellular - sulfate, phosphate and anions of organic molecules - proteins, amino acids, organic acids, which are negatively charged in the usual neutral intracellular environment.

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According to the laws of osmosis and diffusion, ions must move through the membrane in both directions in accordance with the concentration gradient until the concentration is equalized. This, however, does not occur, because at rest the membrane channels are permeable mainly to the ions K+ and Cl- (the hydrated Na+ ion has a larger diameter, and large organic ions do not pass through the membrane at all).

The most labile are K+ ions, which “tend to” leave the cell. This outflow would have to equalize the concentration of K+, but this is prevented by an equivalent, oppositely directed force - the organic anions inside the cell. Therefore, high intracellular K+ concentration cannot significantly change (intracellular K+ should balance the charge of anions). Only a small part of its ions come out, as a result of which an excess of anions is created on the inner surface of the membrane and a negative charge arises, and on the outer surface there is an excess of cations and a positive charge.

Na+ ions passively penetrating into the cell diffuse back (against concentration and electric gradients) extremely weakly. Since an increase in their level in the intracellular fluid is unacceptable, these ions are excreted actively, with the help of an ion sodium pump. The active transport of Na+ from the cell is coupled with the entry of K+ into the cell, which is advantageous from the point of view of energy expenditure. In the conjugate sodium-po- tassium pump, the movement of ions is carried out by carriers, and the latter are transformed with the participation of the metabolic energy of the decomposition of ATP. Due to the hydrolysis energy of one ATP molecule, three Na+ ions are emitted to the outside, and two K+ ions enter the cell. In muscle fibers at rest, 10-20% of the energy resources of the cell are spent on the operation of ion pumps. With frequent excitation in connection with pump activation, these costs increase.

Thus, it can be concluded that the resting potential inherent in the cell is mainly due to the motion of the K+ ions along the con-

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centration gradient. The effect of the negative membrane potential is determined by the combined effect of a high concentration of intracellular non-diffusible anions and a greater or lesser intensity of the transition of mobile negative ions, especially Cl-, into the cells.

The resting potential influences the rate of transmembrane transport of substances (which is important, for example, for the function of the epithelium of the renal tubules), and it is also the basis of the spreading pulse in excitable tissues. The decrease in the magnitude of the membrane potential is called depolarization, and the increase is called hyperpolarization.

The potential of the action is the rapid oscillation (spike) of the membrane potential that arose when excitation of the nerve and muscle cells. It is based on sharp reversible changes in the permeability of the sodium (and potassium) channels of the membrane when the stimulus reaches a certain critical level.

The generation of the action potential is subject to the “all or nothing” law. It arises only at the threshold strength of the stimulation and immediately reaches its maximum value.

When, as a result of depolarization, the membrane potential reaches a threshold value (about -50 mV in a nerve cell), the conformation of the potential-dependent protein molecules that open and close the “gates” of the ion channels changes.

First, the capacity of sodium channels changes, which sharply levels with the increase in the potential of the intracellular environment, i.е. degree of depolarization. Thus, a small initial increase in Na+ ions leads to an increasing avalanche process, as a result of which the permeability of the membrane for Na+ increases to a maximum level (about 500 times) and exceeds its permeability for K+ ions by 20-30 times.

The passive movement of Na+ ions into the cell (the suppressing yield of K+ ions) leads to a very rapid and complete depolarization of the membrane with a subsequent phase of polarity reversal. The membrane potential of the fiber changes from -70 to -40 mV at a

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peak in one millisecond. The outer side of the membrane becomes electrically negative with respect to the internal one.

The described changes correspond to the rising curve (the rising phase) of the registered potential of the action.

After the disappearance of the thermodynamic driving force that facilitates the Na+ input, the sodium channels are spontaneously closed (sodium inactivation) and potassium channels begin to be activated.

K+ ions leave the cell in large quantities, accumulating on the outer surface, as a result of which the membrane potential again becomes negative. Inactivation is also facilitated by an increase in the concentration of Ca++ ions in the cell. In contrast to the Na + channels, the K + channels are devoid of the inactivation mechanism.

During a single action potential through the membrane, an insignificant amount of Na+ and K+ ions passes about one millionth of their content in the cell. When generating a large number of pulses, slightly small ion fluxes can nevertheless substantially change the intracellular Na+ and extracellular K+ concentrations. The prevention of long gradient shifts is realized by the K+ - Na+ pump, which quickly pumped out all Na+ ions entering the cell and exchanges them for K+ ions. In the generation of the nerve impulse, the pump does not participate.

The repolarization phase, corresponding to the descending curve of the action potential, lasts 1-2 milliseconds (ms). At this time, the original resting potential is restored.

The total duration of the action potential in different nerve and skeletal muscle fibers is 0.5-5 ms, in the cells of the heart muscle tens and hundreds of milliseconds.

During depolarization, polarity reversal, and at the beginning of the repolarization phase, the corresponding portion of the membrane temporarily becomes completely unexcavated-refractory. The property of refractoriness is due to the degree of inactivation of sodium channels: the higher this degree, the fuller the refractori-

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ness. Refractivity plays an important role in the excitatory process, limiting the maximum frequency of generation of action potentials and establishing the limiting rhythm of impulse (the measure of “lability” of the tissue according to N.E. Vvedenskiy).

2.3. The spread of the nerve impulse

A feature of the action potential (a nervous impulse) is its selfpropagation along the nerve or muscle fibers. The energy necessary for the transfer of momentum is released in the fiber itself during the decay of ATP.

The spreading nerve impulse provides the transfer of information from the peripheral receptor endings to the nerve centers, and from them to the effector. In muscle cells, the propagating nerve impulse exerts a starting influence on the processes that activate the contractile apparatus.

According to the theory of local currents (L. German, 1879, A. Hodgkin, 1937), the action potential arising at the point of stimulation is not only an indicator of the excitation state of this region, but also a source of stimulation of the neighboring unexcited fiber region. This is due to the appearance of circular, or local, currents between the excited (i.e., negatively charged) and adjacent (positively charged) regions of the membrane.

As a result of the local electrochemical shift of the ion permeability of the membrane, its depolarization arises and a critical threshold potential is obtained, which translates into an action potential. In the zone initially excited, at this time the rest potential is restored. Then the action potential arises on the next section of the fiber, and so on. Therefore, the excitation wave passes along the fiber, not dying and not turning back, because on the next traversed site there is a refractory zone.

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Thus, the spreading (conduction) consists in the sequential occurrence and disappearance of action potentials throughout the nerve or muscle fibers.

Such continuous impulses are characteristic for muscle fiber and non-myelinated nerve fibers, which have only the Schwann membrane, which are few in the nervous system.

In myelinated nerve fibers, except for the Schwann and myelin sheath (which is a good electrical insulator), circular currents can occur only between two neighboring (excited and unexcited) Ranvier intercepts, where myelin is absent. The output of circular currents in the Ranvier interception leads to a depolarization of the membrane and the occurrence of an action potential. Similarly, the next interception is initiated.

The intermittent mechanism of impulse transmission along the fiber has an advantage over the continuous one, as it provides greater speed of measurement, less power consumption and increased reliability (due to high current density at interceptions).

In myelinated nerve fibers, the speed of the pulse is 30-120 m/s, in non-myelinated nerve fibers - 0.5-3.0 m/s, in skeletal muscle fibers - up to 5 m/s.

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