Physiology of parabiosis. The concept of parabiotic agents and their mechanisms of action. The doctrine of N. E. Vvedensky about parabiosis A functional system that ensures the constancy of the blood gas constant. Analysis of its central and peripheral components
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.
Parabiosis (in translation: “para” - about, “bio” - life) is a condition 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, as well as prolonged action of electric current. The doctrine of parabiosis is associated with elucidating the mechanisms of inhibition, which underlies the vital activity of the body
As is known, tissues can be in two functional states - inhibition and excitation. Excitation is an active state of tissue, accompanied by the activity of an organ or system. Inhibition is also an active state of tissue, but characterized by inhibition of the activity of any organ or system of the body. According to Vvedensky, there is one biological process in the body, which has two sides - inhibition and excitation, which proves the doctrine of parabiosis.
Vvedensky’s classic experiments in the study of parabiosis were carried out on a neuromuscular preparation. In this case, a pair of electrodes was used, placed on the nerve, between which a cotton wool moistened with KCl (potassium parabiosis) was placed. During the development of parabiosis, four phases were identified.
1. Phase of short-term increase in excitability. It is rarely captured and lies in the fact that under the influence of a subthreshold stimulus the muscle contracts.
2. Equalizing phase (transformation). It manifests itself in the fact that the muscle responds to frequent and rare stimuli with contractions of the same magnitude. The equalization of the strength of muscle effects occurs, according to Vvedensky, due to the parabiotic site, in which lability decreases under the influence of KCl. So, if lability in the parabiotic area has decreased to 50 pulses/s, then it passes such a frequency, while more frequent signals are delayed in the parabiotic area, since some of them fall into the refractory period, which is created by the previous impulse and therefore, it does not show its effect.
3. Paradoxical phase. It is characterized by the fact that when exposed to frequent stimuli, a weak contractile effect of the muscle is observed or not observed at all. At the same time, in response to rare impulses, a slightly larger muscle contraction occurs than to more frequent ones. The paradoxical reaction of the muscle is associated with an even greater decrease in lability in the parabiotic area, which practically loses the ability to conduct frequent impulses.
4. Braking phase. During this period of tissue condition, neither frequent nor rare impulses pass through the parabiotic area, as a result of which the muscle contracts. Maybe the tissue died in the parabiotic area? If you stop the action of KCl, then the neuromuscular drug gradually restores its function, going through the stages of parabiosis in the reverse order, or act on it with single electrical stimuli, to which the muscle contracts slightly.
According to Vvedensky, in the parabiotic area during the inhibition phase, stationary excitation develops, blocking the conduction of excitation to the muscle. It is the result of the summation of excitation created by KCl irritation and impulses coming from the site of electrical stimulation. According to Vvedensky, the parabiotic site has all the signs of excitation, except one - the ability to spread. As follows, the inhibitory phase of parabiosis reveals the unity of the processes of excitation and inhibition.
According to modern data, the decrease in lability in the parabiotic region is apparently associated with the gradual development of sodium inactivation and closure of sodium channels. Moreover, the more often impulses arrive to it, the more it manifests itself. Parabiotic inhibition is widespread and occurs in many physiological and especially pathological conditions, including the use of various narcotic substances.
NOT. Vvedensky in 1902 he showed that a section of a nerve that has undergone alteration - poisoning or damage - acquires low lability. This means that the state of excitement that arises in this area disappears more slowly than in the normal area. Therefore, at a certain stage of poisoning, when the overlying normal area is exposed to a frequent rhythm of irritation, the poisoned area is not able to reproduce this rhythm, and excitation is not transmitted through it. N.E. Vvedensky called this state of reduced lability parabiosis(from the word “para” - around and “bios” - life), to emphasize that in the area of parabiosis, normal life activity is disrupted.
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., a change in its state was caused 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 section of the nerve or above it, that is, in such a way that impulses arise in the parabiotic section or pass 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 nerve, an increase in the strength of rhythmic stimulation of the nerve leads to an increase in the force of tetanic contraction ( rice. 160, A). With the development of parabiosis, these relationships naturally change, and the following successive stages are observed.
- Provisional, or equalizing, phase. During this initial phase of alteration, the ability of the nerve to conduct rhythmic impulses decreases with any strength of irritation. 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 equal ( rice. 160, B).
- Paradoxical phase follows the equalizing phase and is the most characteristic phase of parabiosis. 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 tetanic contractions ( rice. 160, V).
- Braking phase- the last stage of parabiosis. During this period, the nerve completely loses the ability to conduct excitation of any intensity.
The dependence of the effects of nerve irritation on the strength of the current is due to the fact that as the strength of the stimuli increases, the number of excited nerve fibers increases and the frequency of impulses arising in each fiber increases, since a strong stimulus can cause a volley of impulses.
Thus, the nerve reacts with a high frequency of excitations in response to strong stimulation. With the development of parabiosis, the ability to reproduce frequent rhythms, i.e. lability, decreases. This leads to the development of the phenomena described above.
With low strength or a rare rhythm of stimulation, each impulse generated in an undamaged area of the nerve is also conducted through the parabiotic area, since by the time it arrives in this area, the excitability, reduced after the previous impulse, has time to fully recover.
With strong irritation, when impulses follow each other with high frequency, each subsequent impulse arriving at the parabiotic site enters a stage of relative refractoriness after the previous one. At this stage, the excitability of the fiber is sharply reduced, and the amplitude of the response is reduced. Therefore, spreading excitation does not occur, but only an even greater decrease in excitability occurs.
In the area of parabiosis, impulses coming quickly one after another seem to block their own path. During the equalizing phase of parabiosis, all these phenomena are still weakly expressed, so only a transformation of a frequent rhythm into a rarer one occurs. As a result, the effects of frequent (strong) and relatively rare (moderate) stimulation are equalized, while at the paradoxical stage the cycles of excitability restoration are so prolonged that frequent (strong) stimulation generally turns out to be ineffective.
With particular clarity, these phenomena can be traced on single nerve fibers when they are irritated by stimuli of different frequencies. Thus, I. Tasaki influenced one of the interceptions of Ranvier of the myelinated nerve fiber of a frog with a solution of urethane and studied the conduction of nerve impulses through such an interception. He showed that while rare stimuli passed through the interception unimpeded, frequent ones were blocked by it.
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.
Excitable tissues professor N. E. Vvedensky, studying the work of a neuromuscular drug when exposed to various stimuli.
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Causes of parabiosis
These are 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 the phenomenon 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:
- 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;
- 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;
- Brake, when the muscle did not respond to both strong and weak stimuli by contracting. It is this state of tissue that is referred to as parabiosis.
Biological significance of parabiosis
. For the first time, a similar effect was noticed in cocaine, however, due to toxicity and the ability to cause addiction, safer analogues are currently used - lidocaine and tetracaine. One of Vvedensky’s followers, N.P. Rezvyakov proposed to consider the pathological process as a stage of parabiosis, therefore, for its treatment it is necessary to use antiparabiotic agents.Parabiosis Vvedensky
Concept of parabiosis (para- near, bios
Parabiosis- this is a reversible change that, with deepening and intensification of the action of the agent that caused it, turns into an irreversible disruption of life - death
First stage of parabiosis - provisional
Second stage of parabiosis - paradoxical.
Third stage of parabiosis - brake.
Conclusion :
Parabiosis
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"Vvedensky's Parabiosis"
Parabiosis Vvedensky
N. E. Vvedensky discovered that excitable tissues respond to a wide variety of extremely strong influences (ether, cocaine, direct current, etc.) with a peculiar phase reaction, the same in all cases, which he called parabiosis.
N. E. Vvedensky studied the phenomenon of parabiosis on nerves, muscles, glands, and the spinal cord and came to the conclusion that parabiosis is a general, universal reaction of excitable tissues to strong or prolonged exposure.
Concept ofparabiosis (para- near, bios- life) was introduced into the physiology of the nervous system by N. E. Vvedensky. In 1901, N. E. Vvedensky’s monograph “Excitation, Inhibition and Anesthesia” was published, in which, based on his research, he suggested the unity of the processes of excitation and inhibition.
Parabiosis- this is a reversible change that, with deepening and intensification of the action of the agent that caused it, turns into an irreversible disruption of life - death
The essence of parabiosis is that under the influence of an irritant in excitable tissues, their physiological properties change, first of all, lability sharply decreases.
N. E. Vvedensky’s classic experiments on the study of parabiosis were carried out on a neuromuscular preparation of a frog. The nerve in a small area was damaged (alteration) by chemicals (cocaine, chloroform, phenol, potassium chloride), strong faradic current, and a mechanical factor. Then, irritation with an electric current was applied to the altered area of the nerve or above it.
Thus, the impulses must either originate in the altered segment of the nerve or pass through it on their way to the muscle. The contraction of the muscle indicated the conduction of excitation along the nerve.
First stage of parabiosis - provisional, equalizing, or stage of transformation. 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 one. In the very first stage of parabiosis, a transformation (alteration, translation) of frequent rhythms of excitation into more rare ones is observed. All the described changes in the response of the muscle and the nature of the occurrence of excitation waves in the nerve under the influence of irritation are the result of a weakening of the functional properties, especially lability, in the altered part of the nerve.
Second stage of parabiosis - paradoxical. This stage occurs as a result of ongoing and deepening changes in the functional properties of the parabiotic segment of the nerve. A feature of this stage is the paradoxical relationship of the altered section of the nerve to weak (rare) or strong (frequent) waves of excitation coming here from normal sections of the nerve. Rare waves of excitation pass through the parabiotic segment of the nerve and cause muscle contraction. Frequent waves of excitation either do not occur at all, seem to fade here, which is observed with the full development of this stage, or cause the same contractile effect of the muscle as rare waves of excitation, or less pronounced.
Third stage of parabiosis - brake. 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.
Conclusion :
Parabiosis- the phenomenon is reversible. When the cause of parabiosis is eliminated, the physiological properties of the nerve fiber are restored. In this case, a reverse development of the phases of parabiosis is observed - inhibitory, paradoxical, equalizing.
The presence of electronegativity in the altered part of the nerve allowed N. E. Vvedensky to consider parabiosis as a special type of excitation, localized at the site of its origin and unable to spread.
