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Pflueger's laws. Laws of irritation of excitable tissues

Pflueger's laws. Laws of irritation of excitable tissues

Qualitative and quantitative changes in the processes occurring in the body, respectively, reflect the qualitative and quantitative characteristics of the stimuli acting on it and the method of their action on the body, i.e. irritation.

The smallest strength of the stimulus that causes minimal excitation is called the threshold of irritation. Since the threshold of irritation characterizes excitability, it is at the same time the threshold of excitability. The greater the excitability, the more the threshold of irritation decreases, and, conversely, the lower the excitability, the greater the strength of irritation, which causes the least excitation. The excitability threshold is determined on a neuromuscular specimen by the strength of the direct electric current required to produce a barely noticeable muscle contraction.

The greater the strength of stimulation, the greater, to a certain limit, the excitation and, consequently, the response of the excited one.

The strength of irritation less than the threshold is called subthreshold, and more than the threshold is called suprathreshold. The least force of irritation that causes the greatest tissue response is called maximum. Different increasing values of the decomposition force located between the threshold and the maximum are called submaximal, and those greater than the maximum are called supermaximal.

The threshold of excitability depends on the properties of the excitable tissue, its physiological state at the time of application of irritation, the method and duration of irritation, and the intensity of the irritation.

Law of irritation gradient (accommodation)

In 1848, Dubois-Reymond discovered that if a constant threshold force passes through a nerve or any other tissue and the strength of this current does not change over a significant period of time, then such a current does not excite the tissue during its passage. Excitation occurs only if the electrical stimulus rapidly increases or decreases. With a very slow increase in current strength there is no irritation. The Dubois-Reymond law applies not only to the action of electric current, but also to the action of any other stimulus. This is the law of gradient. The gradient of irritation denotes the rate of increase in the strength of irritation. The greater its increase in each subsequent unit of time, the greater, to a certain limit, the reaction of living tissue to this irritation. The rate of increase in excitation depends on the gradient of stimulation. Excitation increases the more slowly, the smaller the gradient of irritation.

The excitability threshold increases significantly with a slow increase in irritation. It can be assumed that living tissue counteracts external irritation. For example, if you quickly hit a nerve, cool it very quickly, or heat it up with a stimulus strength above the threshold, then excitation occurs. If. slowly pressing on the nerve, slowly cooling or heating it, then excitation is not caused. A low-frequency sinusoidal alternating electric current does not cause excitation because its rate of change is too slow. Consequently, with a slow increase in irritation, adaptation occurs, adaptation of the irritated tissue to the stimulus Sh. S. Betitov, Kh. S. Vorontsov. This adaptation is called accommodation.

The faster the strength of irritation increases, the stronger the arousal is to a certain limit, and vice versa. The rate of accommodation is the lowest rate of increase in the strength of stimulation at which it still causes excitement. This is the threshold gradient of accommodation.

The motor nerves have much greater accommodation than the sensory nerves. The smallest accommodation is in tissues that have automaticity (heart muscle, smooth muscles of the digestive canal and other organs).

Law of hyperbole

To obtain excitation, a certain minimum time of irritation with direct electric current is necessary. There is a certain relationship between the strength of the irritating direct electric current and the time of irritation necessary for the occurrence of excitation, or the latent period. This dependence is expressed by a force-time curve, which has the form of an equilateral hyperbola (Goorweg, 1892, Weiss, 1901).

The law of hyperbole: each minimum period of time of stimulation corresponds to the minimum strength of direct current at which excitation is obtained, and vice versa. In modern times, there are electronic devices that allow tissue to be irritated for thousandths or less of a second or in micro-intervals of time (0.001 s is abbreviated as σ - sigma).

The stronger the current, the shorter the duration of its action required to obtain excitation, and vice versa.

Pfluger's polar law

Pflueger (1859) established that when irritated by a direct electric current, excitation occurs at the moment of its closure or when its strength increases in the area of application of the negative pole to the irritated tissue - the cathode, from where it spreads along the nerve or muscle. At the moment the current opens or when it weakens, excitation occurs in the area of application of the positive pole - the anode. At the same current strength, the excitation is greater when shorting in the cathode region than when opening in the anode region. When irritating a neuromuscular preparation with a direct electric current, different results are obtained depending on its strength and direction. A distinction is made between incoming current direction, in which the anode is located closer to the muscle, and downward direction - if the cathode is located closer to the muscle.

Phenomena of electroton and perielectroton

When a direct current is closed and passes through a nerve or muscle, the physiological and physicochemical properties at the poles change.

When a direct current passes in the area where the cathode is applied, the excitability temporarily increases, and in the area where the anode is applied, the excitability temporarily decreases. Even weak and short-term currents, following an increase in excitability, cause a decrease in excitability in the area of action of the cathode. This subsequent decrease in excitability in this area under the influence of relatively strong and prolonged currents is especially pronounced - cathodic depression (B. F. Verigo, 1888). Cathodic depression can interfere with the conduction of nerve impulses (D. S. Vorontsov, 1937). It disappears 7-8 ms after turning off the DC current.

In the area of action of the cathode, when closed, the speed of excitation increases, and in the area of action of the anode it decreases. In the area of action of the cathode, the height of the excitation wave decreases and its duration increases, and in the area of action of the anode, on the contrary, the height increases and its duration decreases. The duration of complete inexcitability in the area of action of the cathode increases, and that of the anode decreases. Therefore, lability in the area of action of the cathode decreases, and in the area of action of the anode it increases.

These changes in the physiological properties of the nerve in the area of action of the cathode are designated as catelectroton, and in the area of action of the anode - as anelectroton. Changes in the physiological properties of the nerve occur not only at the site of application of the direct current poles, but also at some distance from them. At a distance of about 2 cm outside the cathode, the excitability of the nerve decreases, and outside the anode it increases. This fact was discovered by N. Ya. Perna (1914) and designated it as perielectroton.

Consequently, not only do excitation waves propagate in peripheral nerves, but when a focus of excitation appears at some distance from it, areas of increased and decreased excitability appear and are established along the entire nerve in the form of a stationary wave. Thus, in the peripheral nerves there is a double nerve signaling: impulse and tonic. Some authors deny the existence of perielectroton (D.S. Vorontsov, 1961).

At the points where DC poles are applied, the amount of acetylcholine increases in the area of action of the cathode and decreases in the area of action of the anode, the content of potassium ions in the area of action of the cathode and calcium ions in the area of action of the anode increases relatively, the permeability of protein membranes increases in the area of action of the cathode and their permeability decreases in area of action of the anode.

Changes in nerve excitability under the influence of direct current are also observed in humans. An electrode with a small surface, or indifferent, is applied to the irritated area of the nerve, and an electrode with a large surface, or indifferent, is applied to a distant part of the body. With this unipolar method of stimulation, the effect of the current appears only near the trim electrode. Depending on the current strength, different results are obtained.

With a weak direct current, irritation in the anode region is subthreshold. Therefore, regardless of the direction of the current, contraction occurs only in the cathode region, since the excitation at this pole is greater than at the anode. At an average current strength, irritation in the anode region reaches a threshold. Therefore, regardless of the direction of the current, contractions are obtained both in the cathode region and in the anode region.

With a strong upward current, excitation occurs in the cathode region when it is closed, but it cannot reach the muscle, since anelectroton occurs along the way (a sharp decrease in excitability and conductivity), so contraction occurs only when it is opened. With a strong downward current, the short circuit causes muscle contraction, but when it opens, there is no contraction. This lack of contraction depends on the fact that at the moment of opening in the cathode region, excitability and conductivity sharply decrease and the excitation arising at the anode is not conducted to the muscle.

Law of physiological electroton: the action of direct current on tissue is accompanied by a change in its excitability. When a direct current passes through a nerve or muscle, the threshold of irritation under the cathode and the areas adjacent to it decreases due to depolarization of the membrane - excitability increases. In the area where the anode is applied, the irritation threshold increases, i.e., excitability decreases due to hyperpolarization of the membrane. These changes in excitability under the cathode and anode are called electroton(electrotonic change in excitability). An increase in excitability under the cathode is called catelectroton, and a decrease in excitability under the anode - anelectroton.

With further action of direct current, the initial increase in excitability under the cathode is replaced by its decrease, the so-called cathodic depression. The initial decrease in excitability under the anode is replaced by its increase - anodic exaltation. In this case, in the area of application of the cathode, inactivation of sodium channels occurs, and in the area of action of the anode, there is a decrease in potassium permeability and a weakening of the initial inactivation of sodium permeability. (see notebook lecture 5)

Accommodation– change in the threshold of irritation over time. Accommodation determines an increase in the threshold of stimulation depending on the rate of increase in the strength of the stimulus. If the current increases slowly, it may not cause excitation due to a decrease in tissue excitability. Accommodation is based on the phenomenon of inactivation of sodium and an increase in potassium membrane conductivity.

Different fabrics have different accommodation properties. Accommodation manifests itself especially clearly when direct current acts on the tissue. In this case, the tissue response is observed only when the current circuit is closed and opened.

Pflueger's polar law. – establishes the location of excitation in excitable tissues under the action of direct current:

When the DC circuit is closed, the excitation is under the cathode

When the circuit opens - at the anode

when the current closes, excitation occurs under the cathode, and when it opens, under the anode. The passage of a direct electrical current through a nerve or muscle fiber causes a change in the resting membrane potential. Thus, in the area where the cathode is applied to the excitable tissue, the positive potential on the outer side of the membrane decreases, depolarization occurs, which quickly reaches a critical level and causes excitation. In the area where the anode is applied, the positive potential on the outer side of the membrane increases, hyperpolarization of the membrane occurs and excitation does not occur. But at the same time, under the anode, the critical level of depolarization shifts to the level of the resting potential. Therefore, when the current circuit is opened, the hyperpolarization on the membrane disappears and the resting potential, returning to its original value, reaches a shifted critical level and excitation occurs.

The occurrence of propagating excitation (PD) is possible under the condition that the stimulus acting on the cell has a certain minimum (threshold strength), in other words, when the strength of the stimulus corresponds to the threshold of irritation.

Threshold- this is the smallest amount of stimulus that, acting on the cell for a certain time, is capable of causing maximum excitation.

This is the smallest stimulus value, under the influence of which the resting potential can shift to the level of critical depolarization.

This is the critical value of depolarization of the cell membrane at which the transfer of sodium ions into the cell is activated.

2. Dependence of the threshold strength of the stimulus on its duration.

The threshold strength of any stimulus, within certain limits, is inversely related to its duration. This dependence, discovered by Goorweg, Weiss, and Lapik, was called the “force-duration” or “force-time” curve.

The force-time curve has a shape close to an equilateral hyperbola and, to a first approximation, can be described by the empirical formula:

I= a + b, where I is the current strength

T T – duration of its action

a, b – constants, determined by the properties of the tissue.

From this curve it follows:

A current below the threshold does not cause excitation, no matter how long it lasts.
No matter how strong the stimulus is, if it acts for a very short time, then excitement does not occur.

The minimum current (or voltage) that can cause excitation is called rheobase– (base of current) = threshold.

The minimum time during which a stimulus of one rheobase must act to cause excitation is useful time. Its further increase does not matter for the occurrence of excitation.

Threshold (rheobase)– values are not constant, they depend on the functional state of the cells at rest.

Therefore, Lapik proposed to determine a more accurate indicator - chronaxy.

Chronaxia- the shortest time during which a current of two rheobases must act on the tissue to cause excitation.

Definition of chronaxy – chronaximetry – has become widespread in the clinic for diagnosing damage to nerve trunks and muscles.

3. Dependence of the threshold on the steepness of the stimulus increase (accommodation).

The irritation threshold is the smallest for rectangular shocks of electric current, when the force increases very quickly.

With a decrease in the steepness of the stimulus increase, the processes of inactivation of sodium permeability are accelerated, leading to an increase in the threshold and a decrease in the amplitude of action potentials.

The steeper the current must rise to cause excitation, the higher the speed accommodation.

The rate of accommodation of those formations that are prone to automatic activity (myocardium, smooth muscles) is very low.

3. The “all or nothing” law.

Installed by Bowditch in 1871 on the heart muscle.

With a subthreshold strength of stimulation, the heart muscle does not contract, and with a threshold force of stimulation, the contraction is maximum.

With a further increase in the strength of stimulation, the amplitude of contractions does not increase.

Over time, the relativity of this law was established. It turned out that “everything” depends on the functional state of the tissue (cooling, initial muscle stretch, etc.).

With the advent of microelectrode technology, another discrepancy was established: subthreshold stimulation causes local, non-spreading excitation, therefore, it cannot be said that subthreshold stimulation does not produce anything.

The process of development of excitation obeys this law from the level of critical depolarization, when an avalanche-like flow of potassium ions into the cell is triggered.

4. Changes in excitability when excited.

The measure of excitability is the threshold of irritation. With local, local excitation, excitability increases.

The action potential is accompanied by multiphasic changes in excitability

Period increased excitability corresponds to a local response, when the membrane potential reaches the UCP, excitability is increased.
Period absolute refractoriness corresponds to the depolarization phase of the action potential, the peak and the beginning of the repolarization phase, excitability is reduced until completely absent during the peak.
Period relative refractoriness corresponds to the remainder of the repolarization phase, excitability gradually recovers to its original level.
Supernormal period corresponds to the phase of trace depolarization of the action potential (negative trace potential), excitability is increased.
Subnormal period corresponds to the phase of trace hyperpolarization of the action potential (positive trace potential), excitability is reduced.
Lability (functional mobility).

Lability– the rate of physiological processes in excitable tissue.

For example, we can talk about the maximum frequency of stimulation that excitable tissue is capable of reproducing without rhythm transformation.

A measure of lability can serve:

Duration of a single potential

Absolute refractory phase value

Speed of ascending and descending phases of AP.

Lability level characterizes the rate of occurrence and compensation of excitation in any cells and the level of their functional state.

You can measure the lability of membranes, cells, and organs. Moreover, in a system of several elements (tissues, organs, formations), lability is determined by the area with the least lability:

7. Polar law of irritation (Pflueger's law).

(changes in membrane potential when exposed to direct electric current on excitable tissues).

Pflueger (1859)

Direct current exhibits its irritating effect only at the moment of closing and opening the circuit.
At short circuit DC circuit excitation occurs under the cathode; at opening at the anode.

Change in excitability under the cathode.

When a direct current circuit is closed under the cathode (a subthreshold, but long-lasting stimulus is applied), a persistent long-term depolarization occurs on the membrane, which is not associated with a change in the ionic permeability of the membrane, but is caused by the redistribution of ions outside (introduced at the electrode) and inside - the cation moves to the cathode.

Along with the shift in membrane potential, the level of critical depolarization also shifts to zero. When the direct current circuit under the cathode is opened, the membrane potential quickly returns to the initial level, and the UCD slowly, therefore, the threshold increases, excitability decreases - cathodic depression Verigo. Thus, it occurs only when the DC circuit under the cathode is closed.

Changes in excitability under the anode.

When a direct current circuit is closed under the anode (a subthreshold, long-lasting stimulus), hyperpolarization develops on the membrane due to the redistribution of ions on both sides of the membrane (without changing the ionic permeability of the membrane) and the resulting shift in the level of critical depolarization towards the membrane potential. Consequently, the threshold decreases, excitability increases - anodic exaltation.

When the circuit is opened, the membrane potential quickly recovers to its original level and reaches a reduced level of critical depolarization, and an action potential is generated. Thus, excitation occurs only when the DC circuit under the anode is opened.

Shifts in membrane potential near the DC poles are called electrotonic.

Shifts in membrane potential not associated with changes in the ionic permeability of the cell membrane are called passive.

Polar law of current action. When a nerve or muscle is irritated by direct current, excitation occurs at the moment of closing the direct current only under the cathode, and at the moment of opening - only under the anode, and the threshold of the closing shock is less than the breaking shock. Direct measurements have shown that the passage of electrical current through a nerve or muscle fiber primarily causes a change in the membrane potential under the electrodes. In the area of application to the surface of the anode tissue (+), the positive potential on the outer surface of the membrane increases, i.e. In this area, hyperpolarization of the membrane occurs, which does not contribute to excitation, but, on the contrary, prevents it. In the same area where the cathode (-) is attached to the membrane, the positive potential of the outer surface decreases, depolarization occurs, and if it reaches a critical value, an AP occurs in this place.

MF changes occur not only directly at the points of application of the cathode and anode to the nerve fiber, but also at some distance from them, but the magnitude of these shifts decreases with distance from the electrodes. Changes in MP under the electrodes are called electrotonic(respectively cat-electroton and an-electroton), and behind the electrodes - perielectrotonic(cat- and an-perieelectroton).

An increase in MF under the anode (passive hyperpolarization) is not accompanied by a change in the ionic permeability of the membrane, even at a high applied current. Therefore, when a direct current is closed, excitation does not occur under the anode. In contrast, a decrease in the MF under the cathode (passive depolarization) entails a short-term increase in Na permeability, which leads to excitation.

The increase in membrane permeability to Na upon threshold stimulation does not immediately reach its maximum value. At the first moment, depolarization of the membrane under the cathode leads to a slight increase in sodium permeability and the opening of a small number of channels. When, under the influence of this, positively charged Na+ ions begin to enter the protoplasm, the depolarization of the membrane increases. This leads to the opening of other Na channels, and, consequently, to further depolarization, which, in turn, causes an even greater increase in sodium permeability. This circular process, based on the so-called. positive feedback, called regenerative depolarization. It occurs only when E o decreases to a critical level (E k). The reason for the increase in sodium permeability during depolarization is probably associated with the removal of Ca++ from the sodium gate when electronegativity occurs (or electropositivity decreases) on the outer side of the membrane.

The increased sodium permeability stops after tenths of a millisecond due to sodium inactivation mechanisms.

The rate at which membrane depolarization occurs depends on the strength of the irritating current. At weak strength, depolarization develops slowly, and therefore, for an AP to occur, such a stimulus must have a long duration.

The local response that occurs with subthreshold stimuli, like AP, is caused by an increase in sodium permeability of the membrane. However, under a threshold stimulus, this increase is not large enough to cause a process of regenerative depolarization of the membrane. Therefore, the onset of depolarization is stopped by inactivation and an increase in potassium permeability.

To summarize the above, we can depict the chain of events developing in a nerve or muscle fiber under the cathode of the irritating current as follows: passive depolarization of the membrane ---- increased sodium permeability --- increased flow of Na into the fiber --- active depolarization of the membrane -- local response --- excess Ec --- regenerative depolarization --- action potential (AP).

What is the mechanism for the occurrence of excitation under the anode during opening? At the moment the current is turned on under the anode, the membrane potential increases - hyperpolarization occurs. At the same time, the difference between Eo and Ek grows, and in order to shift the MP to a critical level, greater force is needed. When the current is turned off (opening), the original level of Eo is restored. It would seem that at this time there are no conditions for the occurrence of excitement. But this is only true if the current lasted a very short time (less than 100 ms). With prolonged exposure to current, the critical level of depolarization itself begins to change - it grows. And finally, a moment arises when the new Ek becomes equal to the old level Eo. Now, when the current is turned off, conditions for excitation arise, because the membrane potential becomes equal to the new critical level of depolarization. The PD value when opening is always greater than when closing.

Dependence of threshold stimulus strength on its duration. As already indicated, the threshold strength of any stimulus, within certain limits, is inversely related to its duration. This dependence manifests itself in a particularly clear form when rectangular direct current shocks are used as a stimulus. The curve obtained in such experiments was called the “force-time curve.” It was studied by Goorweg, Weiss and Lapik at the beginning of the century. From an examination of this curve, it follows first of all that a current below a certain minimum value or voltage does not cause excitation, no matter how long it lasts. The minimum current strength capable of causing excitation is called rheobase by Lapik. The shortest time during which an irritating stimulus must act is called useful time. Increasing the current leads to a shortening of the minimum stimulation time, but not indefinitely. With very short stimuli, the force-time curve becomes parallel to the coordinate axis. This means that with such short-term irritations, excitation does not occur, no matter how great the strength of irritation.

Determining useful time is practically difficult, since the point of useful time is located on a section of the curve that turns into parallel. Therefore, Lapik proposed using the useful time of two rheobases - chronaxy. Its point is located on the steepest section of the Goorweg-Weiss curve. Chronaximetry has become widespread both experimentally and clinically for diagnosing damage to motor nerve fibers.

Dependence of the threshold on the steepness of the increase in stimulus strength. The threshold value for irritation of a nerve or muscle depends not only on the duration of the stimulus, but also on the steepness of the increase in its strength. The irritation threshold has the smallest value for rectangular current impulses, characterized by the fastest possible increase in current. If, instead of such stimuli, linearly or exponentially increasing stimuli are used, the thresholds turn out to be increased and the more slowly the current increases, the greater. When the slope of the current increase decreases below a certain minimum value (the so-called critical slope), the PD does not occur at all, no matter to what final strength the current increases.

This phenomenon of adaptation of excitable tissue to a slowly increasing stimulus is called accommodation. The higher the rate of accommodation, the more steeply the stimulus must increase in order not to lose its irritating effect. Accommodation to a slowly increasing current is due to the fact that during the action of this current in the membrane processes have time to develop that prevent the occurrence of AP.

It was already indicated above that depolarization of the membrane leads to the onset of two processes: one fast, leading to an increase in sodium permeability and the occurrence of AP, and the other slow, leading to inactivation of sodium permeability and the end of excitation. With a steep increase in stimulus, Na activation has time to reach a significant value before Na inactivation develops. In the case of a slow increase in current intensity, inactivation processes come to the fore, leading to an increase in the threshold and a decrease in the AP amplitude. All agents that enhance or accelerate inactivation increase the rate of accommodation.

Accommodation develops not only when excitable tissues are irritated by electric current, but also when mechanical, thermal and other stimuli are used. Thus, a quick blow to a nerve with a stick causes its excitation, but when slowly pressing on the nerve with the same stick, no excitation occurs. An isolated nerve fiber can be excited by rapid cooling, but not by slow cooling. A frog will jump out if thrown into water with a temperature of 40 degrees, but if the same frog is placed in cold water and slowly heated, the animal will cook, but will not react by jumping to a rise in temperature.

In the laboratory, an indicator of the speed of accommodation is the smallest slope of the current increase at which the stimulus still retains the ability to cause AP. This minimum slope is called critical slope. It is expressed either in absolute units (mA/sec) or in relative ones (as the ratio of the threshold strength of that gradually increasing current, which is still capable of causing excitation, to the rheobase of a rectangular current impulse).

The "all or nothing" law. When studying the dependence of the effects of stimulation on the strength of the applied stimulus, the so-called "all or nothing" law. According to this law, under threshold stimuli they do not cause excitation ("nothing"), but under threshold stimuli, excitation immediately acquires a maximum value ("all"), and no longer increases with further intensification of the stimulus.

This pattern was initially discovered by Bowditch while studying the heart, and was later confirmed in other excitable tissues. For a long time, the "all or nothing" law was incorrectly interpreted as a general principle of the response of excitable tissues. It was assumed that “nothing” meant a complete absence of response to a subthreshold stimulus, and “everything” was considered as a manifestation of the complete exhaustion of the excitable substrate’s potential capabilities. Further studies, especially microelectrode studies, showed that this point of view is not true. It turned out that at subthreshold forces, local non-propagating excitation (local response) occurs. At the same time, it turned out that “everything” also does not characterize the maximum that PD can achieve. In a living cell, there are processes that actively stop membrane depolarization. If the incoming Na current, which ensures the generation of AP, is weakened by any influence on the nerve fiber, for example, drugs, poisons, then it ceases to obey the “all or nothing” rule - its amplitude begins to gradually depend on the strength of the stimulus. Therefore, “all or nothing” is now considered not as a universal law of the response of an excitable substrate to a stimulus, but only as a rule, characterizing the features of the occurrence of AP in given specific conditions.

The concept of excitability. Changes in excitability when excited.

Excitability parameters.

Excitability is the ability of a nerve or muscle cell to respond to stimulation by generating PD. The main measure of excitability is usually rheobase. The lower it is, the higher the excitability, and vice versa. This is due to the fact that, as we said earlier, the main condition for the occurrence of excitation is the achievement of a critical level of depolarization by the MF (Eo<= Ек). Поэтому мерилом возбудимости является разница между этими величинами (Ео - Ек). Чем меньше эта разница, тем меньшую силу надо приложить к клетке, чтобы сдвинуть мембранный потенциал до критического уровня, и, следовательно, тем больше возбудимость клетки.

Pflueger also showed that excitability is a variable quantity. The cathode increases excitability, the anode decreases it. Let us recall that these changes in excitability under the electrodes are called electrotonic. The Russian scientist Verigo showed that with prolonged exposure to direct current on the tissue, or under the influence of strong stimuli, these electrotonic changes in excitability are perverted - under the cathode, the initial increase in excitability is replaced by its decrease (the so-called cathodic depression develops), and under the anode, the reduced excitability gradually increases . The reason for these changes in excitability at the poles of direct current is due to the fact that the value of Ek changes with prolonged exposure to the stimulus. Under the cathode (and during excitation), Ek gradually moves away from the MP and decreases, so that a moment comes when the difference E0-Ek becomes greater than the initial one. This leads to a decrease in tissue excitability. On the contrary, under the anode Ek tends to increase, gradually approaching Eo. In this case, excitability increases, as the initial difference between Eo and Ek decreases.

The reason for the change in the critical level of depolarization under the cathode is the inactivation of sodium permeability due to prolonged depolarization of the membrane. At the same time, permeability to K increases significantly. All this leads to the fact that the cell membrane loses its ability to respond to irritating stimuli. The same changes in the membrane underlie the already discussed phenomenon of accommodation. Under the anode, under the action of current, the inactivation phenomena are reduced.

Changes in excitability when excited. The occurrence of AP in a nerve or muscle fiber is accompanied by multiphase changes in excitability. To study them, a nerve or muscle is exposed to two short electrical stimuli following each other at a certain interval. The first is called annoying, the second - testing. Registration of PDs arising in response to these irritations made it possible to establish important facts.

During a local response, excitability is increased, since the membrane is depolarized and the difference between E0 and Ek falls. The period of occurrence and development of the peak of the action potential corresponds to the complete disappearance of excitability, called absolute refractoriness (unimpressiveness). At this time, the testing stimulus is not capable of causing a new PD, no matter how strong this irritation is. The duration of absolute refractoriness approximately coincides with the duration of the ascending branch of AP. In fast-conducting nerve fibers it is 0.4-0.7 ms. In the fibers of the heart muscle - 250-300 ms. Following absolute refractoriness, the phase begins relative refractoriness , which lasts 4-8 ms. It coincides with the AP repolarization phase. At this time, excitability gradually returns to its original level. During this period, the nerve fiber is able to respond to strong stimulation, but the amplitude of the action potential will be sharply reduced.

According to the Hodgkin-Huxley ion theory, absolute refractoriness is caused first by the presence of maximum sodium permeability, when a new stimulus cannot change or add anything, and then by the development of sodium inactivation, which closes Na channels. This is followed by a decrease in sodium inactivation, as a result of which the ability of the fiber to generate AP is gradually restored. This is a state of relative refractoriness.

The relative refractory phase is replaced by the phase elevated (supernormal) ) excitability And, coinciding in time with the period of trace depolarization. At this time, the difference between Eo and Ek is lower than the original one. In motor nerve fibers of warm-blooded animals, the duration of the supernormal phase is 12-30 ms.

The period of increased excitability is replaced by a subnormal phase, which coincides with trace hyperpolarization. At this time, the difference between the membrane potential (Eo) and the critical level of depolarization (Ek) increases. The duration of this phase is several tens or hundreds of ms.

Lability. We examined the basic mechanisms of the occurrence and propagation of a single excitation wave in nerve and muscle fibers. However, in the natural conditions of an organism’s existence, not single, but rhythmic volleys of action potentials pass through nerve fibers. In sensitive nerve endings located in any tissue, rhythmic discharges of impulses arise and spread along the afferent nerve fibers extending from them, even with very short-term stimulation. Likewise, from the central nervous system along the efferent nerves there is a flow of impulses to the periphery to the executive organs. If the executive organ is skeletal muscles, then flashes of excitation occur in them in the rhythm of impulses arriving along the nerve.

The frequency of impulse discharges in excitable tissues can vary widely depending on the strength of the applied stimulation, the properties and condition of the tissue, and the speed of individual acts of excitation in a rhythmic series. To characterize this speed, N.E. Vvedensky formulated the concept of lability. Under lability, or functional mobility he understood the greater or lesser rate of occurrence of those elementary reactions that accompany excitation. A measure of lability is the largest number of action potentials that an excitable substrate is capable of reproducing per unit time in accordance with the frequency of applied stimulation.

Initially it was assumed that the minimum interval between impulses in a rhythmic series should correspond to the duration of the absolute refractory period. Precise studies, however, have shown that with a repetition frequency of stimuli with such an interval, only two impulses arise, and the third drops out due to developing depression. Therefore, the interval between pulses should be slightly greater than the absolute refractory period. In the motor nerve cells of warm-blooded animals, the refractory period is about 0.4 msec, and the potential maximum rhythm should be equal to 2500/sec, but in fact it is about 1000/sec. It should be emphasized that this frequency significantly exceeds the frequency of impulses passing through these fibers under physiological conditions. The latter is about 100/sec.

The fact is that usually in natural conditions the tissue works with the so-called optimal rhythm. To transmit impulses with such a rhythm, a great force of stimulation is not required. Studies have shown that the frequency of stimulation and the rheobase of the current capable of causing nerve impulses with such a frequency are in a peculiar relationship: the rheobase first falls as the frequency of the impulses increases, then increases again. The optimum is for nerves in the range from 75 to 150 pulses/sec, for muscles - 20-50 pulses/sec. This rhythm, unlike others, can be reproduced very persistently and for a long time by excitable formations.

Thus, we can now name all the main parameters of tissue excitability that characterize its properties: RHEOBASE, USEFUL TIME (CHRONAXY), CRITICAL SLOPE, LABILITY. All of them, except the last one, are in inversely proportional relationships with excitability.

The concept of "parabiosis""Lability is not a constant quantity. It can change depending on the state of the nerve or muscle, depending on the strength and duration of irritations falling on them, on the degree of fatigue, etc. For the first time, a change in the lability of a nerve when it is exposed first to chemicals and then and electrical stimuli, studied by N.E. Vvedensky. He discovered a natural decrease in the lability of a nerve section altered by a chemical agent (ammonia), called this phenomenon “parabiosis" and studied its patterns. Parabiosis is a reversible condition, which, however, with the deepening of the action of the causing its agent may become irreversible.

Vvedensky considered parabiosis as a special state of persistent, unfluctuating excitation, as if frozen in one section of the nerve fiber. Indeed, the parabiotic site is negatively charged. Vvedensky considered this phenomenon to be a prototype of the transition of excitation to inhibition in nerve centers. In his opinion, parabiosis is the result of overexcitation of a nerve cell by too much or too frequent stimulation.

The development of parabiosis occurs in three stages: equalizing, paradoxical and inhibitory. Initially, due to a decrease in accommodation, individual current pulses of low frequency, provided they are of sufficient strength, no longer produce 1 pulse, but 2,3 or even 4. At the same time, the threshold of excitability increases, and the maximum rhythm of excitation progressively decreases. As a result, the nerve begins to respond to impulses of both low and high frequencies with the same frequency of discharges, which is closest to the optimal rhythm for this nerve. That's what it is equalization phase parabiosis. At the next stage of development of the process, in the region of threshold intensities of stimulation, the reproduction of a rhythm close to optimal is still preserved, and the tissue either does not respond to frequent impulses at all, or responds with very rare waves of excitation. This - paradoxical phase.

Then the ability of the fiber for rhythmic wave activity decreases, the amplitude of the AP also decreases, and its duration increases. Any external influence reinforces the state of inhibition of the nerve fiber and at the same time inhibits itself. This is the last one braking phase parabiosis.

Currently, the described phenomenon is explained from the perspective of the membrane theory by a violation of the mechanism of increasing sodium permeability and the appearance of prolonged sodium inactivation. As a result of this, Na channels remain closed, it accumulates in the cell and the outer surface of the membrane retains a negative charge for a long time. This prevents new irritation by lengthening the refractory period. When approaching a site of parabiosis with frequently successive APs, the inactivation of sodium permeability caused by the altering agent is added to the inactivation that accompanies the nerve impulse. As a result, excitability is reduced so much that the conduction of the next impulse is completely blocked.

Metabolism and energy during excitement. When excitation occurs and occurs in nerve cells and muscle fibers, metabolism increases. This is manifested both in a number of biochemical changes occurring in the membrane and protoplasm of cells, and in an increase in their heat production. It has been established that when excited, the following occurs: increased breakdown in cells of energy-rich compounds - ATP and creatine phosphate (CP), increased processes of breakdown and synthesis of carbohydrates, proteins and lipids, increased oxidative processes, leading in combination with glycolysis to the resynthesis of ATP and CP, synthesis and destruction of acetylcholine and norepinephrine, other mediators, increased synthesis of RNA and proteins. All these processes are most pronounced during the period of restoration of the membrane state after PD.

In nerves and muscles, each wave of excitation is accompanied by the release of two portions of heat, of which the first is called initial, and the second - delayed heat. The initial heat generation occurs at the moment of excitation and constitutes an insignificant part of the total heat production (2-10%) during excitation. It is assumed that this heat is associated with those physicochemical processes that develop at the moment of generation of PD. Delayed heat generation occurs over a longer period of time, lasting many minutes. It is associated with those chemical processes that occur in the tissue following a wave of excitation, and, in the figurative expression of Ukhtomsky, constitute the “metabolic tail of the comet of excitation.”

Carrying out stimulation. Classification of nerve fibers. As soon as an AP occurs at any point in a nerve or muscle fiber and this area acquires a negative charge, an electric current arises between the excited and neighboring resting sections of the fiber. In this case, the excited section of the membrane acts on neighboring sections as a direct current cathode, causing their depolarization and generating a local response. If the magnitude of the local response exceeds the Ec of the membrane, PD occurs. As a result, the outer surface of the membrane becomes negatively charged in the new area. In this way, the excitation wave propagates along the entire fiber at a speed of about 0.5-3 m/sec.

Laws of conduction of excitation along nerves.

1. Law of Physiological Continuity . Cutting, ligating, as well as any other impact that disrupts the integrity of the membrane (physiological, and not just anatomical), creates non-conductivity. The same thing occurs with thermal and chemical influences.

2. Law of two-way conduct . When irritation is applied to a nerve fiber, excitation spreads along it in both directions (along the surface of the membrane - in all directions) at the same speed. This is proven by the experience of Babukhin and others like him.

3. Law of isolated conduction . In a nerve, impulses propagate along each fiber separately, i.e. do not transfer from one fiber to another. This is very important as it ensures precise addressing of the pulse. This is due to the fact that the electrical resistance of the myelin and Schwann sheaths, as well as the intercellular fluid, is much greater than the resistance of the nerve fiber membrane.

The mechanisms and speed of excitation in the non-pulpal and pulpal nerve fibers are different. In the pulpless excitation extends continuously along the entire membrane from one excited area to another located nearby, as we have already discussed.

In myelin fibers, excitation spreads only spasmodically, jumping over areas covered with the myelin sheath (saltatory). Action potentials in these fibers arise only at the nodes of Ranvier. At rest, the outer surface of the excitable membrane of all nodes of Ranvier is positively charged. At the moment of excitation, the surface of the first interception becomes negatively charged with respect to the adjacent second interception. This leads to the emergence of a local electric current that flows through the intercellular fluid, membrane and axoplasm surrounding the fiber from interception 2 to 1. The current emerging through interception 2 excites it, causing the membrane to recharge. Now this section can excite the next one, etc.

Jumping of the AP over the interinterceptual area is possible because the amplitude of the AP is 5-6 times greater than the threshold required to excite not only the next one, but also 3-5 interceptions. Therefore, microdamage to the fiber in the interinterceptor areas or in more than one interception does not stop the functioning of the nerve fiber until the regenerative phenomena involve 3 or more adjacent Schwann cells.

The time required for the transfer of excitation from one interception to another is the same for fibers of different diameters, and is 0.07 ms. However, since the length of the interstitial sections is different and proportional to the diameter of the fiber, in myelinated nerves the speed of nerve impulses is directly proportional to their diameter.

Classification of nerve fibers. The electrical response of an entire nerve is the algebraic sum of the PD of its individual nerve fibers. Therefore, on the one hand, the amplitude of the electrical impulses of the whole nerve depends on the strength of the stimulus (as it increases, more and more fibers are involved), and secondly, the total action potential of the nerve can be divided into several separate oscillations, the reason for which is the unequal speed of impulse conduction along the different fibers that make up the whole nerve.

Currently, nerve fibers are usually divided into three main types based on the speed of excitation, the duration of various phases of action activity, and structure.

Fiber type A are divided into subgroups (alpha, beta, gamma, delta). They are covered with a myelin sheath. Their conduction speed is the highest - 70-120 m/sec. These are motor fibers from the motor neurons of the spinal cord. The remaining type A fibers are sensitive.

Fiber type IN- myelin, mainly preganglionic. Conduction speed - 3-18 m/sec.

Fiber type WITH - pulpless, very small in diameter (2 microns). The speed of conduction is no more than 3 m/sec. These are most often postganglionic fibers of the sympathetic nervous system.

Rice. 8. Force-duration curve.

The strength-duration curve has a shape close to a hyperbola; those. in a certain range, the dependence of the threshold strength of the stimulus on its duration is inversely related. The less time the stimulus acts on the excitable tissue, the higher its strength is required to initiate excitation.

The minimum current (or voltage) that can cause excitation is called rheobase. The shortest time during which a stimulus of one rheobase must act to cause excitation is the useful time. Its further increase does not matter for the occurrence of excitation.

Two important consequences of the law of time:

1. A current below the threshold does not cause excitation, no matter how long it lasts.

2. No matter how strong the stimulus is, if it acts for a very short time, then excitement does not occur.

The threshold (rheobase) is a variable value and depends on the functional state of the cells at rest. Therefore, Lapik proposed to determine a more accurate indicator - chronaxy.

Chronaxy is the time during which a current in two rheobases must act on the tissue to cause excitation. The definition of chronaxy - chronaximetry - has become widespread in the clinic for diagnosing damage to nerve trunks and muscles.

7.3. Dependence of the threshold on the steepness of the stimulus increase (gradient law).

The irritation threshold is the smallest for rectangular shocks of electric current, when the force increases very quickly.

With a decrease in the steepness of the stimulus increase, a accommodation(due to inactivation of sodium permeability), the irritation threshold increases (decreased excitability). Those. to obtain excitation, the magnitude of the stimulus must be greater than if it increased instantly (Fig. 9).

Rice. 9. Gradient law (accommodation).

The steeper the current must increase to cause excitation, the higher the rate of accommodation.

The minimum gradient is the minimum rate of increase of the stimulus at which excitable tissue is still capable of responding with excitation to this stimulus. Tissue with higher excitability tends to accommodate faster and therefore has a higher minimum gradient.

In practice, based on the existence of the gradient law, rectangular electrical stimuli are usually used to apply electrical stimulation to excitable tissue - i.e. stimuli that have a very high rising edge.

The “all or nothing” law.

Installed by Bowditch in 1871 on the heart muscle. With a subthreshold strength of stimulation, the heart muscle does not contract, and with a threshold force of stimulation, the contraction is maximum. With a further increase in the strength of stimulation, the amplitude of contractions does not increase.

Over time, the universality of this law was established in relation to all excitable tissues. However, studies using microelectrode technology have also revealed some formal inconsistency: subthreshold stimulation causes local, non-spreading excitation, therefore, it cannot be said that subthreshold stimulation does not produce anything.

The process of development of excitation obeys this law with CUD, when an avalanche-like entry of sodium ions into the cell is triggered.

7.5. Polar law of irritation (Pflueger's law).

Pfluger's laws (1859) are based on changes in membrane potential when excitable tissue is exposed to direct electric current (Fig. 10).

Rice. 10. The effect of electric current on excitable tissues.

A – change in the MF under the cathode with a short-term passage of current; B – with long-term current flow; B – occurrence of PD at a threshold current value; G – change in the MF under the anode with a short-term passage of current; D - change in MP and CUD under prolonged action of a strong anode current - anode-break excitation.

1. Direct current exhibits its irritating effect only at the moment of closing and opening the circuit.

2. When the DC circuit is closed, excitation occurs under the cathode; when opening under the anode.