The use of parabiosis in zootechnical practice. Parabiosis and its stages. Correlation of excitability phases with phases of action potential and single contraction

Nerve fibers have lability- the ability to reproduce a certain number of excitation cycles per unit of time in accordance with the rhythm of existing stimuli. A measure of lability is the maximum number of excitation cycles that a nerve fiber can reproduce per unit time without transforming the rhythm of stimulation. Lability is determined by the duration of the peak of the action potential, i.e., the phase of absolute refractoriness. Since the duration of absolute refractoriness of the spike potential of a nerve fiber is the shortest, its lability is the highest. A nerve fiber can reproduce up to 1000 impulses per second.

Phenomenon parabiosis discovered by the Russian physiologist N.E. Vvedensky in 1901 while studying the excitability of a neuromuscular drug. The state of parabiosis can be caused by various influences - ultra-frequent, super-strong stimuli, poisons, drugs and other influences, both normally and in pathology. N. E. Vvedensky discovered that if a section of a nerve is subjected to alteration (i.e., exposure to a damaging agent), then the lability of such a section sharply decreases. Restoration of the initial state of the nerve fiber after each action potential in the damaged area occurs slowly. When this area is exposed to frequent stimuli, it is unable to reproduce the given rhythm of stimulation, and therefore the conduction of impulses is blocked. This state of reduced lability was called N. E. Vvedensky parabiosis. The state of parabiosis of excitable tissue occurs under the influence of strong stimuli and is characterized by phase disturbances in conductivity and excitability. There are 3 phases: primary, the phase of greatest activity (optimum) and the phase of reduced activity (pessimum). The third phase combines 3 successively replacing each other stages: equalizing (provisional, transformative - according to N.E. Vvedensky), paradoxical and inhibitory.

The first phase (primum) is characterized by a decrease in excitability and an increase in lability. In the second phase (optimum), excitability reaches a maximum, lability begins to decrease. In the third phase (pessimum), excitability and lability decrease in parallel and 3 stages of parabiosis develop. The first stage - equalizing according to I.P. Pavlov - is characterized by equalization of responses to strong, frequent and moderate irritations. IN equalization phase the magnitude of the response to frequent and rare stimuli is equalized. Under normal conditions of functioning of a nerve fiber, the magnitude of the response of the muscle fibers innervated by it obeys the law of force: the response to rare stimuli is less, and to frequent stimuli it is greater. Under the action of a parabiotic agent and with a rare rhythm of stimulation (for example, 25 Hz), all excitation impulses are conducted through the parabiotic area, since the excitability after the previous impulse has time to recover. With a high stimulation rhythm (100 Hz), subsequent impulses can arrive at a time when the nerve fiber is still in a state of relative refractoriness caused by the previous action potential. Therefore, some impulses are not carried out. If only every fourth excitation is carried out (i.e. 25 impulses out of 100), then the amplitude of the response becomes the same as for rare stimuli (25 Hz) - the response equalizes.

The second stage is characterized by a perverted response - strong irritations cause a smaller response than moderate ones. In this - paradoxical phase there is a further decrease in lability. At the same time, a response occurs to rare and frequent stimuli, but to frequent stimuli it is much less, since frequent stimuli further reduce lability, lengthening the phase of absolute refractoriness. Consequently, a paradox is observed - the response to rare stimuli is greater than to frequent ones.

IN braking phase lability is reduced to such an extent that both rare and frequent stimuli do not cause a response. In this case, the nerve fiber membrane is depolarized and does not enter the repolarization stage, i.e., its original state is not restored. Neither strong nor moderate irritations cause a visible reaction; inhibition develops in the tissue. Parabiosis is a reversible phenomenon. If the parabiotic substance does not act for long, then after its action ceases, the nerve exits the state of parabiosis through the same phases, but in the reverse order. However, under the influence of strong stimuli, the inhibitory stage may be followed by a complete loss of excitability and conductivity, and subsequently tissue death.

The works of N.E. Vvedensky on parabiosis played an important role in the development of neurophysiology and clinical medicine, showing the unity of the processes of excitation, inhibition and rest, and changed the prevailing law of force relations in physiology, according to which the stronger the stimulus, the greater the reaction.

The phenomenon of parabiosis underlies drug local anesthesia. The effect of anesthetic substances is associated with a decrease in lability and a disruption of the mechanism of excitation along nerve fibers.

4. Lability- functional mobility, the speed of elementary cycles of excitation in nervous and muscle tissues. The concept of "L." introduced by the Russian physiologist N. E. Vvedensky (1886), who considered the measure of L. to be the highest frequency of tissue irritation reproduced by it without converting the rhythm. L. reflects the time during which the tissue restores its performance after the next cycle of excitation. The greatest L. is distinguished by the processes of nerve cells - axons, capable of reproducing up to 500-1000 impulses per second; the central and peripheral points of contact - synapses - are less labile (for example, a motor nerve ending can transmit no more than 100-150 excitations per second to the skeletal muscle). Inhibition of the vital activity of tissues and cells (for example, by cold, drugs) reduces L., since this slows down the recovery processes and lengthens the refractory period.

Parabiosis- a state borderline between life and death of a cell.

Causes of parabiosis– a variety of damaging effects on excitable tissue or cells that do not lead to gross structural changes, but to one degree or another disrupt its functional state. Such reasons may be mechanical, thermal, chemical and other irritants.

The essence of parabiosis. As Vvedensky himself believed, the basis of parabiosis is a decrease in excitability and conductivity associated with sodium inactivation. Soviet cytophysiologist N.A. Petroshin believed that parabiosis was based on reversible changes in protoplasmic proteins. Under the influence of a damaging agent, a cell (tissue), without losing its structural integrity, completely stops functioning. This condition develops in phases, as the damaging factor acts (that is, it depends on the duration and strength of the acting stimulus). If the damaging agent is not removed in time, biological death of the cell (tissue) occurs. If this agent is removed in time, the tissue also returns to its normal state in phases.

Experiments by N.E. Vvedensky.

Vvedensky conducted experiments on a frog neuromuscular preparation. Test stimuli of varying strengths were sequentially applied to the sciatic nerve of the neuromuscular preparation. One stimulus was weak (threshold strength), that is, it caused a minimal contraction of the calf muscle. The other stimulus was strong (maximal), that is, the smallest of those that cause maximum contraction of the gastrocnemius muscle. Then, at some point, a damaging agent was applied to the nerve and every few minutes the neuromuscular preparation was tested: alternately with weak and strong stimuli. At the same time, the following stages developed successively:

1. Equalization when in response to a weak stimulus the magnitude of muscle contraction did not change, but in response to a strong stimulus the amplitude of muscle contraction sharply decreased and became the same as in response to a weak stimulus;

2. Paradoxical when, in response to a weak stimulus, the magnitude of the muscle contraction remained the same, and in response to a strong stimulus, the magnitude of the contraction amplitude became smaller than in response to a weak stimulus, or the muscle did not contract at all;

3. Brake, when the muscle did not respond to both strong and weak stimuli by contracting. It is this state of tissue that is designated as parabiosis.

PHYSIOLOGY OF THE CENTRAL NERVOUS SYSTEM

1. Neuron as a structural and functional unit of the central nervous system. Its physiological properties. Structure and classification of neurons.

Neurons– this is the main structural and functional unit of the nervous system, which has specific manifestations of excitability. A neuron is capable of receiving signals, processing them into nerve impulses and conducting them to nerve endings that contact another neuron or reflex organs (muscle or gland).

Types of neurons:

1. Unipolar (have one process - an axon; characteristic of invertebrate ganglia);

2. Pseudounipolar (one process dividing into two branches; typical for ganglia of higher vertebrates).

3. Bipolar (there is an axon and a dendrite, typical for peripheral and sensory nerves);

4. Multipolar (axon and several dendrites - typical for the vertebrate brain);

5. Isopolar (it is difficult to differentiate the processes of bi- and multipolar neurons);

6. Heteropolar (it is easy to differentiate the processes of bi- and multipolar neurons)

Functional classification:

1. Afferent (sensitive, sensory - perceive signals from the external or internal environment);

2. Intercalary neurons connecting each other (provide information transfer within the central nervous system: from afferent neurons to efferent ones).

3. Efferent (motor, motor neurons - transmit the first impulses from the neuron to the executive organs).

home structural feature neuron – the presence of processes (dendrites and axons).

1 – dendrites;

2 – cell body;

3 – axon hillock;

4 – axon;

5 – Schwann cell;

6 – Ranvier interception;

7 – efferent nerve endings.

The sequential synoptic combination of all 3 neurons forms reflex arc.

Excitation, which arises in the form of a nerve impulse on any part of the membrane of a neuron, runs across its entire membrane and along all its processes: both along the axon and along the dendrites. Transmitted excitation from one nerve cell to another only in one direction- from axon transmitting neuron per perceiver neuron via synapses located on its dendrites, body or axon.

Synapses provide one-way transmission of excitation. A nerve fiber (neuron extension) can transmit nerve impulses in both directions, and one-way transmission of excitation appears only in nerve circuits, consisting of several neurons connected by synapses. It is synapses that provide one-way transmission of excitation.

Nerve cells perceive and process information coming to them. This information comes to them in the form of control chemicals: neurotransmitters . It can be in the form stimulating or brake chemical signals, as well as in the form modulating signals, i.e. those that change the state or operation of the neuron, but do not transmit excitation to it.

The nervous system plays an exceptional role integrating role in the life activity of the organism, since it unites (integrates) it into a single whole and integrates it into the environment. It ensures the coordinated functioning of individual parts of the body ( coordination), maintaining a balanced state in the body ( homeostasis) and adaptation of the body to changes in the external or internal environment ( adaptive state and/or adaptive behavior).

A neuron is a nerve cell with processes, which is the main structural and functional unit of the nervous system. It has a structure similar to other cells: membrane, protoplasm, nucleus, mitochondria, ribosomes and other organelles.

There are three parts in a neuron: the cell body - the soma, the long process - the axon, and many short branched processes - the dendrites. The soma performs metabolic functions, the dendrites specialize in receiving signals from the external environment or from other nerve cells, the axon conducts and transmits excitation to an area remote from the dendrite zone. An axon ends in a group of terminal branches to transmit signals to other neurons or executive organs. Along with the general similarity in the structure of neurons, there is great diversity due to their functional differences (Fig. 1).

There are a number of laws that excitable tissues obey: 1. The law of “force”; 2. The “all or nothing” law; 3. The law of “force - time”; 4. Law of “slope of current rise”; 5. Law of “polar action of direct current”.

Law of “force” The greater the strength of the stimulus, the greater the magnitude of the response. For example, the magnitude of skeletal muscle contraction, within certain limits, depends on the strength of the stimulus: the greater the strength of the stimulus, the greater the magnitude of skeletal muscle contraction (until the maximum response is achieved).

The “all or nothing” law The response does not depend on the strength of stimulation (threshold or above-threshold). If the strength of the stimulus is below the threshold, then the tissue does not react (“nothing”), but if the force has reached the threshold value, then the response is maximum (“everything”). According to this law, for example, the heart muscle contracts, which reacts with a maximum contraction already to the threshold (minimum) force of stimulation.

Law of "force - time" The response time of tissue depends on the strength of stimulation: the greater the strength of the stimulus, the less time it must act to cause excitation of the tissue and vice versa.

Law of “accommodation” To cause excitement, the stimulus must increase quickly enough. Under the action of a slowly increasing current, excitation does not occur, since the excitable tissue adapts to the action of the stimulus. This phenomenon is called accommodation.

Law of “polar action” of direct current When exposed to direct current, excitation occurs only at the moment of closing and opening the circuit. When closing - under the cathode, and when opening - under the anode. The excitation under the cathode is greater than under the anode.

Physiology of the nerve trunk Based on their structure, myelinated and non-myelinated nerve fibers are distinguished. In myelin - excitation spreads spasmodically. In unmyelinated ones - continuously along the entire membrane, using local currents.

Laws of conduction of excitation according to the present day 1. Law of two-way conduction of excitation: excitation along a nerve fiber can spread in two directions from the place of its irritation - centripetally and centrifugally. 2. The law of isolated conduction of excitation: each nerve fiber that is part of the nerve conducts excitation in isolation (PD is not transmitted from one fiber to another). 3. The law of anatomical and physiological integrity of the nerve fiber: for excitation to occur, the anatomical (structural) and physiological (functional) integrity of the nerve fiber is necessary.

The doctrine of parabiosis Developed by N. E. Vvedensky in 1891 Phases of parabiosis Equalizing Paradoxical Inhibitory

The neuromuscular synapse is a structural and functional formation that ensures the transmission of excitation from the nerve fiber to the muscle fiber. The synapse consists of the following structural elements: 1 - presynaptic membrane (this is the part of the membrane of the nerve ending that is in contact with the muscle fiber); 2 - synaptic cleft (its width is 20 -30 nm); 3 - postsynaptic membrane (end plate); At the nerve ending there are numerous synaptic vesicles containing a chemical mediator for the transmission of excitation from nerve to muscle - a mediator. At the neuromuscular synapse, the mediator is acetylcholine. Each vesicle contains about 10,000 molecules of acetylcholine.

Stages of neuromuscular transmission The first stage is the release of acetylcholine (ACh) into the synaptic cleft. It begins with depolarization of the presynaptic membrane. At the same time, Ca channels are activated. Calcium enters the nerve ending along a concentration gradient and promotes the release of acetylcholine from synaptic vesicles into the synaptic cleft by exocytosis. Second stage: the transmitter (ACh) reaches the postsynaptic membrane by diffusion, where it interacts with the cholinergic receptor (ChR). The third stage is the emergence of excitation in the muscle fiber. Acetylcholine interacts with the cholinergic receptor on the postsynaptic membrane. In this case, chemoexcitable Na channels are activated. The flow of Na+ ions from the synaptic cleft into the muscle fiber (along the concentration gradient) causes depolarization of the postsynaptic membrane. An end plate potential (EPP) occurs. The fourth stage is the removal of ACh from the synaptic cleft. This process occurs under the action of the enzyme acetylcholinesterase.

Resynthesis of ACh For transmission of one AP across a synapse, about 300 vesicles with ACh are required. Therefore, constant restoration of ACh reserves is necessary. Resynthesis of ACh occurs: Due to breakdown products (choline and acetic acid); New synthesis of mediator; Delivery of necessary components along the nerve fiber.

Disruption of synaptic conduction Some substances can partially or completely block neuromuscular transmission. The main ways of blocking: a) blockade of the conduction of excitation along the nerve fiber (local anesthetics); b) disruption of acetylcholine synthesis in the presynaptic nerve ending, c) inhibition of acetylcholinesterase (FOS); d) binding of the cholinergic receptor (-bungarotoxin) or long-term displacement of ACh (curare); inactivation of receptors (succinylcholine, decamethonium).

Motor Units Each muscle fiber has a motor neuron attached to it. As a rule, 1 motor neuron innervates several muscle fibers. This is the motor (or motor) unit. Motor units differ in size: the volume of the motor neuron body, the thickness of its axon and the number of muscle fibers included in the motor unit.

Muscle physiology Muscle functions and their significance. Physiological properties of muscles. Types of muscle contraction. The mechanism of muscle contraction. Work, strength and muscle fatigue.

18 Functions of muscles There are 3 types of muscles in the body (skeletal, cardiac, smooth), which carry out movement in space Mutual movement of body parts Maintaining posture (sitting, standing) Heat production (thermoregulation) Movement of blood, lymph Inhalation and exhalation Movement of food in the gastrointestinal tract Protection internal organs

19 Properties of muscles M. have the following properties: 1. Excitability; 2. Conductivity; 3. Contractility; 4. Elasticity; 5. Extensibility.

20 Types of muscle contractions: 1. Isotonic - when contraction changes the length of the muscles (they shorten), but the tension (tone) of the muscles remains constant. Isometric contractions are characterized by an increase in muscle tone, while the length of the muscle does not change. Auxotonic (mixed) - contractions in which both the length and tone of the muscles change.

21 Types of muscle contractions: There are also single and tetanic muscle contractions. Single contractions occur in response to the action of rare single impulses. At a high frequency of irritating impulses, a summation of muscle contractions occurs, which causes prolonged shortening of the muscle - tetanus.

Serrated tetanus Occurs when each subsequent impulse falls within the period of relaxation of a single muscle contraction

Smooth tetanus Occurs when each subsequent impulse falls into the period of shortening of a single muscle contraction.

31 Mechanism of muscle contraction (gliding theory): Transfer of excitation from nerve to muscle (through the neuromuscular synapse). Distribution of PD along the muscle fiber membrane (sarcolemma) and deep into the muscle fiber along T-tubules (transverse tubules - recesses of the sarcolemma into the sarcoplasm) Release of Ca++ ions from the lateral cisterns of the sarcoplasmic reticulum (calcium depot) and its diffusion to the myofibrils. Interaction of Ca++ with the protein troponin located on actin filaments. Release of binding sites on actin and contact of myosin cross bridges with these areas of actin. Release of ATP energy and sliding of actin filaments along myosin filaments. This leads to shortening of the myofibril. Next, the calcium pump is activated, which ensures active transport of Ca from the sarcoplasm to the sarcoplasmic reticulum. The concentration of Ca in the sarcoplasm decreases, resulting in relaxation of the myofibril.

Muscle strength The maximum load that a muscle lifts, or the maximum tension that it develops during its contraction, is called muscle strength. It is measured in kilograms. The strength of a muscle depends on the thickness of the muscle and its physiological cross-section (this is the sum of the cross-sections of all the muscle fibers that make up that muscle). In muscles with longitudinally located muscle fibers, the physiological cross-section coincides with the geometric one. In muscles with oblique fibers (pinnate type muscles), the physiological cross-section significantly exceeds the geometric cross-section. They belong to the power muscles.

Types of muscles A - parallel B - feathery C - fusiform

Muscle work When lifting a load, the muscle performs mechanical work, which is measured by the product of the mass of the load and the height of its lifting and is expressed in kilograms. A = F x S, where F is the mass of the load, S is the height of its lifting If F = 0, then work A = 0 If S = 0, then work A = 0 Maximum muscle work is performed under average loads (the law of “average” loads).

Fatigue is a temporary decrease in muscle performance as a result of prolonged, excessive loads, which disappears after rest. Fatigue is a complex physiological process associated primarily with fatigue of the nerve centers. According to the theory of “clogging” (E. Pfluger), a certain role in the development of fatigue is played by the accumulation of metabolic products (lactic acid, etc.) in the working muscle. According to the theory of “exhaustion” (K. Schiff), fatigue is caused by the gradual depletion of energy reserves (ATP, glycogen) in working muscles. Both of these theories are formulated on the basis of data obtained in experiments on isolated skeletal muscle and explain fatigue in a one-sided and simplified way.

Theory of active rest Until now, there is no single theory explaining the causes and essence of fatigue. Under natural conditions, fatigue of the body's musculoskeletal system is a multifactorial process. I.M. Sechenov (1903), using an ergograph he designed for two hands to study the performance of muscles when lifting a load, found that the performance of a tired right hand is restored more fully and quickly after active rest, that is, rest accompanied by work of the left hand. Thus, active rest is a more effective means of combating muscle fatigue than simple rest. Sechenov associated the reason for the restoration of muscle performance in conditions of active rest with the effect on the central nervous system of afferent impulses from muscle and tendon receptors of working muscles.

STRUCTURE OF SODIUM CHANNELS

Na + -voltage-dependent channels of plasma membranes are very complex protein complexes that have a wide variety of forms in different tissues. They have the general property of being highly sensitive to the inhibitory effects of tetrodotoxin (TTX) and saxitoxin (STX). They are an integral protein (M 260,000 - 320,000) consisting of α- and β-subunits. The main properties of the channel are determined by the α-subunit, which has 4 similar fragments, each of which is represented by 6 transmembrane domains, which form a pseudosymmetric structure that crosses the lipid bilayer. In the center of such a structure there is a pore resembling a cylinder through which sodium ions pass. On the inside, the pore is lined with negatively charged amino acids, and the role of potential sensor is performed by amino acids (arginine and lysine) that carry a positive charge.

Rice. 2. Two-dimensional model of a voltage-dependent sodium channel. The model assumes the presence of 4 domains, each of which consists of 6 transmembrane α-helices of the protein. The α-helices of domain IV are sensitive to changes in membrane potential. Their movement in the plane of the membrane (conformation) transfers the channel to an active (open) state. The intracellular loop between domains III and IV functions as a closing gating mechanism. The selective filter is part of the extracellular loop between helices 5 and 6 of domain IV.

Also, the α-subunit has in its structure an amino acid sequence homologous to the “EF-hand” of Ca-binding proteins, such as calmodulin. They have two types of control gates - activation (m-gate) and inactivation (h-gate).

Rice. 3. Cell membrane. Sodium channel.

Under conditions of functional rest (Emp = - 80 mV), the activation gate is closed, but is ready to open at any moment, and the inactivation gate is open. When the membrane potential decreases to -60 mV, the activation gate opens, allowing Na + ions to pass through the channel into the cell, but soon the inactivation gate begins to close, causing inactivation of the sodium channel and the passage of ions through the channel. Some time later, the activation gate closes, and the inactivation gate, as the membrane repolarizes, opens, and the channel is ready for a new cycle of operation.

STAGES OF PARABIOSIS

There are three stages of parabiosis: equalizing, paradoxical and inhibitory.

In the normal functional state of excitable tissue, the reproduction of frequent and rare action potentials occurs without change. In an area that has been subjected to prolonged exposure to a stimulus (alteration), due to impaired reactivation of sodium channels, the development of the action potential slows down. As a result, part of the action potentials running at a high frequency (strong excitation) is “quenched” in the altered area. Rare action potentials (weak excitation) are reproduced without change, since there is still enough time for the reactivation of sodium channels at a low frequency in the first phase of parabiosis. Therefore, strong and weak excitation pass through the parabiotic area in almost the same frequency rhythm, the first occurs – equalization phase.

As the inactivation of sodium channels deepens, a phase begins when action potentials with a rare rhythm of stimulation pass through the alteration site, and with a frequent rhythm of stimulation cause an even greater impairment in the reactivation of sodium channels and are practically not reproduced—the onset of paradoxical phase.

Rice. 4. Parabiosis. 1-background contraction, 2-equalizing phase, 3-paradoxical phase, 4-inhibitory phase.

Ultimately, complete inactivation of sodium channels develops; Conductivity in the area subjected to alteration completely disappears, and both strong and weak excitation can no longer pass through it. The braking phase begins parabiosis . Thus, with the development of parabiosis, the excitability, conductivity and lability of excitable tissue decreases and its accommodation increases.

Lability(from Latin labilis - sliding, unstable). Functional mobility, the property of excitable tissues to reproduce without distortion the frequency of applied rhythmic stimuli. A measure of lability is the maximum number of impulses that a given structure can transmit per unit of time without distortion. The term was proposed by N.E. Vvedensky in 1886. Neurons from different areas of the central nervous system differ greatly in lability. For example, motor neurons of the spinal cord usually reproduce frequencies no higher than 200-300 Hz, and interneurons - up to 1000 Hz. As a rule, the lability of the axon of a neuron is much higher than the lability of the body of the same neuron.

Excitability– the ability of tissues to perceive the effects of stimuli and respond to them with an excitation reaction. Excitability is associated with the specific sensitivity of cell membranes, with their ability to respond to the action of adequate stimuli by changes in ionic permeability and membrane potential. A quantitative characteristic of excitability is the excitation threshold, which is characterized by the threshold strength of the stimulus - the minimum force capable of causing a response in excitable tissue. The higher the excitation threshold, the greater the threshold strength of the stimulus and the less excitability of the tissue.

Accommodation(from Latin accomodatio - device). Accustoming excitable tissue to the action of a slowly increasing or constantly acting stimulus. The basis of accommodation is the gradual deepening inactivation of sodium channels. The threshold of excitability during accommodation increases, and the excitability of the tissue decreases accordingly. Inactivation of sodium channels occurs as a consequence of prolonged depolarization caused by subthreshold stimuli. It develops according to the same laws as Verigo cathodic depression during prolonged operation of direct current when the circuit is closed at the cathode.

Conductivity– the ability of excitable tissue to conduct excitation. It is quantitatively characterized by the speed of excitation propagation per unit time (m/s, km/h, etc.).

Refractoriness(French Refractaire - unreceptive) - a short-term decrease in the excitability of nerve and muscle tissue during and after an action potential.

A feature of the parabiotic process, along with its persistence and continuity, is its ability to deepen under the influence of incoming excitation impulses. Therefore, the stronger and more often the arriving impulses, the more they deepen the state of local excitation in the parabiotic area and the more they complicate further conduction.

Parabiosis is a reversible phenomenon. When the altering agent is removed, excitability, lability and conductivity in this area are restored. In this case, all phases of parabiosis occur in the reverse order (inhibitory, paradoxical, equalizing).

MEDICAL ASPECTS OF THE THEORY OF PARABIOSIS

Many physiological states of humans and animals, such as the development of sleep and hypnotic states, can be explained from the standpoint of parabiosis. In addition, the functional significance of parabiosis is determined by the mechanism of action of certain drugs. Thus, the action of local anesthetics (novocaine, lidocaine, etc.), analgesics, and inhalation anesthesia is based on this phenomenon.

Local anesthetics(from the Greek an - negation, aesthesis - sensitivity) reversibly reduce the excitability of sensory nerve endings and block the conduction of impulses in nerve conductors at the site of direct application. These substances are used to relieve pain. A drug from this group, cocaine, was first isolated in 1860 by Albert Niemann from the leaves of the South American shrub Erythroxylon coca. In 1879 V.K. Anrep, a professor at the Military Medical Academy of St. Petersburg, confirmed the ability of cocaine to cause anesthesia. In 1905, E. Eindhorn synthesized and used novocaine for local anesthesia. Lidocaine has been used since 1948.

Local anesthetics consist of a hydrophilic and a lipophilic part, which are connected by ether or alkyd bonds. The biologically (physiologically) active part is the lipophilic structure that forms the aromatic ring.

The mechanism of action of local anesthetics is based on disruption of the permeability of fast voltage-gated sodium channels. These substances bind to open sodium channels during action potentials and cause their inactivation. Local anesthetics do not interact with closed channels during the resting potential and channels that are in an inactivated state during the development of the repolarization phase of the action potential.

Receptors for local anesthetics are located in the S 6 segment IV domain of the intracellular part of sodium channels. In this case, the action of local anesthetics reduces the permeability of activated sodium channels. This in turn causes an increase in the excitation threshold, and ultimately, a decrease in tissue excitability. In this case, a decrease in the number of action potentials and the speed of excitation is observed. As a result, a block for the conduction of nerve impulses is formed in the area where local anesthetics are applied.

According to one theory, the mechanism of action of inhalation anesthesia is also described from the perspective of the theory of parabiosis. NOT. Vvedensky believed that inhalation anesthetics act on the nervous system as strong irritants, causing parabiosis. In this case, a change occurs in the physicochemical properties of the membrane and a change in the activity of ion channels. All these processes cause the development of parabiosis with a decrease in lability, conductivity of neurons and the central nervous system as a whole.

Currently, the term parabiosis is used in particular to describe pathological and extreme conditions.

An example of a pathological condition is experimental neuroses. They develop as a result of overstrain in the cerebral cortex of the main nervous processes - excitation and inhibition, their strength and mobility. Neuroses with repeated overstrain of higher nervous activity can occur not only acutely, but also chronically over many months or years.

Neuroses are characterized by a violation of the basic properties of the nervous system, which normally determine the relationship between the processes of irritation and excitation. As a result, weakening of the functioning of nerve cells, imbalance, etc. may be observed. In addition, neuroses are characterized by phase states. Their essence lies in the disorder between the action of the stimulus and the response.

Phase phenomena can occur not only in pathological conditions, but also very briefly, for several minutes, during the transition from wakefulness to sleep. In neurosis, the following phases are distinguished:

1. Equalization

In this phase, all conditioned stimuli, regardless of their strength, give the same response.

2. Paradoxical

In this case, weak stimuli give a strong effect, and strong ones give the least effect.

3. Ultraparadoxical

The phase when positive stimuli begin to act as negative ones, and vice versa, i.e. there is a distortion of the reaction of the cerebral cortex to the action of stimuli.

4. Brake

It is characterized by a weakening or complete disappearance of all conditioned reflex reactions.

However, it is not always possible to observe a strict sequence in the development of phase phenomena. Phase phenomena in neuroses coincide with the phases previously discovered by N.E. Vvedensky on a nerve fiber during its transition to a parabiotic state.

Parabiosis(in translation: “para” - about, “bio” - life) is a state on the verge of life and death of tissue that occurs when it is exposed to toxic substances such as drugs, phenol, formaldehyde, various alcohols, alkalis and others, and also long-term electric current. The doctrine of parabiosis is associated with elucidating the mechanisms of inhibition, which underlies the vital activity of the body (I.P. Pavlov called this problem “a damned question of physiology”).

Parabiosis develops in pathological conditions when the lability of the structures of the central nervous system decreases or a very massive simultaneous excitation of a large number of afferent pathways occurs, as, for example, during traumatic shock.

The concept of parabiosis was introduced into physiology by Nikolai Evgenievich Vvedensky. In 1901, his monograph “Excitation, Inhibition and Anesthesia” was published, in which the author, based on his research, suggested the unity of the processes of excitation and inhibition.

N. E. Vvedensky showed in 1902 that a section of a nerve that has undergone alteration - poisoning or damage - acquires low lability. This state of reduced lability N.E. Vvedensky called it parabiosis (from the word “para” - near and “bios” - life) to emphasize that in the area of ​​parabiosis normal life activity is disrupted.

N. E. Vvedensky considered parabiosis as a special state of persistent, unwavering excitation, as if frozen in one section of the nerve fiber. He believed that the waves of excitation coming to this area from the normal parts of the nerve, as it were, sum up with the “stationary” excitation present here and deepen it. N. E. Vvedensky considered this phenomenon as a prototype of the transition of excitation to inhibition in nerve centers. Inhibition, according to N. E. Vvedensky, is the result of “overexcitation” of a nerve fiber or nerve cell.

Parabiosis- this is a reversible change that, when the action of the agent that caused it deepens and intensifies, turns into an irreversible disruption of life - death.

The classic experiments of N. E. Vvedensky were carried out on a neuromuscular preparation of a frog. The nerve under study was subjected to alteration in a small area, i.e. caused a change in its state under the influence of the application of any chemical agent - cocaine, chloroform, phenol, potassium chloride, strong faradic current, mechanical damage, etc. Irritation was applied either to the poisoned area of ​​the nerve or above it, so that the impulses originated in the parabiotic area or passed through it on their way to the muscle. N. E. Vvedensky judged the conduction of excitation along a nerve by muscle contraction.

In a normal neuromuscular specimen, an increase in the strength of rhythmic stimulation of the nerve leads to an increase in the force of muscle contraction. With the development of parabiosis, these relationships naturally change.

The following stages of parabiosis are observed:

1. Equalizing, or provisional, phase. This stage of parabiosis precedes the others, hence its name - provisional. It is called equalizing because during this period of development of the parabiotic state, the muscle responds with contractions of the same amplitude to strong and weak irritations applied to the area of ​​the nerve located above the altered area. In the first stage of parabiosis, a transformation (alteration, translation) of frequent rhythms of excitation into more rare ones is observed. However, as Vvedensky showed, this decrease affects the effects of stronger stimuli more sharply than more moderate ones: as a result of this, the effects of both are almost equalized.

2. The paradoxical phase follows the equalizing phase and is the most characteristic phase of parabiosis. This stage occurs as a result of ongoing and deepening changes in the functional properties of the parabiotic segment of the nerve. According to N. E. Vvedensky, it is characterized by the fact that strong excitations emerging from normal points of the nerve are not transmitted at all to the muscle through the anesthetized area or cause only initial contractions, while very moderate excitations are capable of causing quite significant muscle contractions.

Rice. 2. Paradoxical stage of parabiosis. Neuromuscular preparation of a frog during developing parabiosis 43 minutes after lubricating the nerve area with cocaine. Strong irritations (at 23 and 20 cm distance between the coils) produce rapidly passing contractions, while weak irritations (at 28, 29 and 30 cm) continue to cause long-lasting contractions (according to N. E. Vvedensky)

3. The inhibitory phase is the last stage of parabiosis. A characteristic feature of this stage is that in the parabiotic part of the nerve not only excitability and lability are sharply reduced, but it also loses the ability to conduct weak (rare) waves of excitation to the muscle.