Skeletal muscle tension. Mechanism of muscle contractions briefly

text_fields

arrow_upward

In resting muscle fibers, in the absence of motor neuron firing, transverse myosin bridges are not attached to actin myofilaments. Tropomyosin is located in such a way that it blocks actin sites that can interact with myosin cross-bridges. Troponin inhibits myosin - ATP-ase activity and therefore ATP is not split. Muscle fibers are in a relaxed state.

When the muscle contracts, the length of the A-disks does not change, the J-disks shorten, and the H-zone of the A-disks may disappear (Fig. 4.3.).

Fig.4.3. Muscle contraction. A - Cross bridges between actin and myosin are open. The muscle is in a relaxed state.
B - Closing of transverse bridges between actin and myosin. Commitment by the heads of the bridges of rowing movements towards the center of the sarcomere. Sliding of actin filaments along myosin filaments, shortening of the sarcomere, development of traction.

These data were the basis for the creation of a theory explaining muscle contraction by the sliding mechanism. (slip theory) thin actin myofilaments along thick myosin. As a result, myosin myofilaments are drawn between the surrounding actin myofilaments. This leads to a shortening of each sarcomere, and hence the entire muscle fiber.

Molecular mechanism of contraction muscle fiber consists in the fact that the action potential arising in the region of the end plate propagates through the system of transverse tubules deep into the fiber, causes depolarization of the membranes of the sarcoplasmic reticulum cisterns and the release of calcium ions from them. Free calcium ions in the interfibrillar space trigger the contraction process. The set of processes that cause the propagation of the action potential deep into the muscle fiber, the release of calcium ions from the sarcoplasmic reticulum, the interaction of contractile proteins and the shortening of the muscle fiber are called "electromechanical interface". The time sequence between the appearance of the action potential of the muscle fiber, the flow of calcium ions to the myofibrils and the development of fiber contraction is shown in Figure 4.4.

Fig.4.4. Development timeline diagram
action potential (AP), release of calcium ions (Ca2+) and development of isometric muscle contraction.

When the concentration of Ca 2+ ions in the intermyofibrillar space is below 10″, tropomyosin is located in such a way that it blocks the attachment of transverse myosin bridges to actin filaments. The cross bridges of myosin do not interact with actin filaments. There is no movement of actin and myosin filaments relative to each other. Therefore, the muscle fiber is in a relaxed state. When the fiber is excited, Ca 2+ leaves the cisterns of the sarcoplasmic reticulum and, consequently, its concentration near the myofibrils increases. Under the influence of activating Ca 2+ ions, the troponin molecule changes its shape in such a way that it pushes tropomyosin into the groove between two actin filaments, thereby freeing up sites for attachment of myosin cross-bridges to actin. As a result, cross bridges attach to actin filaments. Since the myosin heads make "stroke" movements towards the center of the sarcomere, actin myofilaments are "pulled" into the gaps between the thick myosin filaments and the muscle is shortened.

Energy source for muscle contraction

text_fields

arrow_upward

ATP is the energy source for muscle contraction. With the inactivation of troponin by calcium ions, the catalytic sites for the breakdown of ATP on the myosin heads are activated. The enzyme myosin ATPase hydrolyzes the ATP located on the head of the myosin, which provides energy for the cross bridges. The ADP molecule and inorganic phosphate released during ATP hydrolysis are used for the subsequent resynthesis of ATP. A new ATP molecule is formed on the myosin cross bridge. In this case, the transverse bridge is disconnected from the actin filament. Reattachment and detachment of the bridges continues until the calcium concentration within the myofibrils decreases to a subthreshold value. Then the muscle fibers begin to relax.

With a single movement of the transverse bridges along the actin filaments (stroke movements), the sarcomere is shortened by approximately 1% of its length. Therefore, for a complete isotonic contraction of the muscle, it is necessary to perform about 50 such rowing movements. Only the rhythmic attachment and detachment of the myosin heads can draw the actin filaments along the myosin filaments and accomplish the required shortening of the whole muscle. The tension developed by the muscle fiber depends on the number of simultaneously closed transverse bridges. The rate of development of tension or shortening of the fiber is determined by the frequency of closing of the transverse bridges formed per unit time, that is, the rate of their attachment to actin myofilaments. With an increase in the speed of muscle shortening, the number of simultaneously attached transverse bridges at each moment of time decreases. This can explain the decrease in the force of muscle contraction with an increase in the speed of its shortening.

With a single contraction, the process of shortening of the muscle fiber ends after 15-50 ms, since the calcium ions that activate it return to the cisterns of the sarcoplasmic reticulum with the help of a calcium pump. Muscle relaxation occurs.

Since the return of calcium ions to the cisterns of the sarcoplasmic reticulum goes against the diffusion gradient, this process requires energy. Its source is ATP. One ATP molecule is spent on the return of 2 calcium ions from the interfibrillar space to the cisterns. With a decrease in the content of calcium ions to a subthreshold level (below 10 V), the troponin molecules take on a shape characteristic of the resting state. At the same time, tropomyosin again blocks the sites for attaching cross bridges to actin filaments. All this leads to relaxation of the muscle until the next flow of nerve impulses arrives, when the process described above is repeated. Thus, calcium in muscle fibers plays the role of an intracellular mediator linking the processes of excitation and contraction.

Modes and types of muscle contractions

text_fields

arrow_upward

3.1. Single cut

The mode of contraction of muscle fibers is determined by the frequency of impulses of motor neurons. The mechanical response of a muscle fiber or individual muscle to a single stimulation of them is calledsingle contraction .

With a single reduction, they distinguish:

1. The phase of stress development or shortening;

2. The phase of relaxation or lengthening (Fig. 4.5.).

Fig.4.5. Time development of the action potential (A) and isometric contraction of the adductor thumb muscle (B).
1 - phase of voltage development; 2 - relaxation phase.

The relaxation phase lasts about twice as long as the tension phase. The duration of these phases depends on the morphological and functional properties of the muscle fiber: in the most rapidly contracting fibers of the eye muscles, the tension phase is 7–10 ms, and in the slowest fibers of the soleus muscle, it is 50–100 ms.

Under natural conditions, the muscle fibers of the motor unit and the skeletal muscle as a whole operate in a single contraction mode only when the duration of the interval between successive motor neuron impulses is equal to or exceeds the duration of a single contraction of the muscle fibers innervated by it. Thus, the mode of single contraction of slow fibers of the human soleus muscle is provided at a motor neuron impulse frequency of less than 10 imp/s, and fast fibers of the oculomotor muscles - at a motoneuron impulse frequency of less than 50 imp/s.

In the mode of a single contraction, the muscle is able to work for a long time without developing fatigue. However, due to the fact that the duration of a single contraction is short, the tension developed by the muscle fibers does not reach the maximum possible values. With a relatively high frequency of motor neuron firing, each subsequent irritating impulse falls on the phase of the previous fiber tension, that is, until the moment when it begins to relax. In this case, the mechanical effects of each previous contraction are summed up with the next one. Moreover, the magnitude of the mechanical response to each subsequent pulse is less than the previous one. After the first few impulses, subsequent responses of muscle fibers do not change the tension achieved, but only maintain it. This reduction mode is calledsmooth tetanus (Fig.4.6.). In this mode, the motor units of human muscles work with the development of maximum isometric efforts. With smooth tetanus, the tension developed by DE is 2-4 times greater than with single contractions.

Fig.4.6. Single (a) and tetanic (b, c, d, e) contractions of the skeletal muscle. Superimposition of contraction waves on each other and the formation of tetanus at stimulation frequencies: 5-15 times / s; c — 20 times/s; d — 25 times/s; e - more than 40 times in 1 second (smooth tetanus).

In cases where the intervals between successive impulses of a motor neuron are less than the time of a complete cycle of a single contraction, but more than the duration of the tension phase, the force of contraction DE fluctuates. This reduction mode is called tooth chat tetanus (Fig. 4.6.).

Smooth tetanus for fast and slow mice is achieved at different motoneuron firing rates. It depends on the time of a single contraction. Thus, smooth tetanus for the fast oculomotor muscle appears at frequencies above 150–200 pulses/s, and for the slow soleus muscle, at a frequency of about 30 pulses/s. In the mode of tetanic contraction, the muscle is able to work only for a short time. This is explained by the fact that due to the lack of a period of relaxation, she cannot restore her energy potential and works, as it were, “in debt”.

Mechanical reaction of the whole muscle when it is excited

The mechanical reaction of the whole muscle during its excitation is expressed in two forms - in the development of tension and in shortening. Under natural conditions of activity in the human body, the degree of muscle shortening can be different.

By size shortening There are three types of muscle contraction:

1. Isotonic- this is a contraction of the muscle, in which its fibers are shortened with a constant external load. In real movements, a purely isotonic contraction is practically absent;

2. Isometric is a type of muscle activation in which it develops tension without changing its length. Isometric contraction is at the heart of static work;

3. Auxotonic or anisotonic type- this is the mode in which the muscle develops tension and shortens. It is these contractions that take place in the body during natural locomotion - walking, running, etc.

3.2. Dynamic reduction

Isotonic and anisotonic types of contraction underlie dynamic work human locomotor apparatus.

In dynamic work, there are:

1. Concentric type of contraction- when the external load is less than the tension developed by the muscle. At the same time, it shortens and causes movement;

2. Eccentric type of contraction- when the external load is greater than the muscle tension. Under these conditions, the muscle, tensing, nevertheless stretches (lengthens), while performing negative (inferior) dynamic work

Muscle shortening is the result of the contraction of multiple sarcomeres. When the actin filaments are shortened, they slide relative to the myosin filaments, as a result of which the length of each sarcomere of the muscle fiber decreases. In this case, the length of the threads themselves remains unchanged. Myosin filaments have transverse protrusions (cross bridges) about 20 nm long. Each protrusion consists of a head, which is connected to the myosin filament through a "neck" (Fig. 23).

In a relaxed state, the muscles of the head of the transverse bridges cannot interact with actin filaments, since their active sites (the places of mutual contact with the heads) are isolated by tropomyosin. Shortening of the muscle is the result of conformational changes in the transverse bridge: its head tilts by bending the “neck”.

Rice. 23. Spatial organization of contractile and regulatory proteins in striated muscle. The position of the myosin bridge (stroke effect, the neck is bent) is shown in the process of interaction of contractile proteins in the muscle fiber (fiber contraction)

Process sequence , providing muscle fiber contraction(electromechanical interface):

1. After the occurrence PD in the muscle fiber near the synapse (due to the electric field of the PCP) excitation spreads across the myocyte membrane, including the membranes of the transverse T-tubules. The mechanism of AP conduction along a muscle fiber is the same as that along an unmyelinated nerve fiber - the resulting AP near the synapse, through its electric field, ensures the emergence of new APs in the adjacent section of the fiber, etc. (continuous conduction of excitation).

2. Potential actions T-tubules due to its electric field activates voltage-gated calcium channels on membrane SPR, as a result of which Ca 2+ leaves the SPR tanks according to the electrochemical gradient.

3. In the interfibrillar space Ca 2+ contacts with troponin, which leads to its conformation and displacement of tropomyosin, resulting in actin filaments active areas are exposed with which they are connected heads of myosin bridges.

4. As a result of interaction with actin ATPase activity of the heads of myosin filaments is enhanced, providing the release of ATP energy, which is spent on flexion of the myosin bridge outwardly resembling the movement of oars when rowing (rowing movement) (see Fig. 23), providing sliding of actin filaments relative to myosin filaments. It takes the energy of one ATP molecule to complete one stroke. In this case, the strands of contractile proteins are displaced by 20 nm. The attachment of a new ATP molecule to another part of the myosin head leads to the termination of its engagement, but the energy of ATP is not consumed. In the absence of ATP, the myosin heads cannot break away from actin - the muscle is tense; such, in particular, is the mechanism of rigor mortis.

5. After that the heads of the cross bridges, due to their elasticity, return to their original position and establish contact with the next actin site; then another rowing movement and sliding of actin and myosin filaments occurs again. Such elementary acts are repeated many times. One stroke (one step) causes a decrease in the length of each sarcomere by 1%. With a contraction of an isolated frog muscle without load of 50%, the shortening of sarcomeres occurs in 0.1 s. This requires 50 rowing movements. Myosin bridges bend asynchronously, but due to the fact that there are many of them and each myosin filament is surrounded by several actin filaments, muscle contraction occurs smoothly.

Relaxation muscle is due to processes occurring in reverse order. Repolarization of the sarcolemma and T-tubules leads to the closure of calcium voltage-gated channels of the SPR membrane. Ca-pumps return Ca 2+ to the SPR (the activity of the pumps increases with an increase in the concentration of free ions).

A decrease in the concentration of Ca 2+ in the interfibrillar space causes a reverse conformation of troponin, as a result of which tropomyosin filaments isolate the active sites of actin filaments, which makes it impossible for the heads of myosin cross-bridges to interact with them. Sliding of actin filaments along myosin filaments in the opposite direction occurs under the action of gravitational forces and elastic traction of muscle fiber elements, which restores the original dimensions of sarcomeres.

The source of energy for ensuring the work of skeletal muscles is ATP, the costs of which are significant. Even under the conditions of the main exchange for the functioning of the muscles, the body affects about 25% of all its energy resources. Energy costs increase dramatically during the performance of physical work.

The reserves of ATP in the muscle fiber are insignificant (5 mmol / l) and can provide no more than 10 single contractions.

Energy consumption ATP is required for the following processes.

First, the energy of ATP is spent to ensure the operation of the Na/K pump (it maintains the concentration gradient of Na + and K + inside and outside the cell, which form PP and PD, which provides electromechanical coupling) and the operation of the Ca pump, which lowers the concentration of Ca 2 + in the sarcoplasm after contraction of the muscle fiber, which leads to relaxation.

Secondly, the energy of ATP is spent on the rowing movement of myosin bridges (their bending).

ATP resynthesis carried out with the help of three energy systems of the body.

1. The phosphogenic energy system provides ATP resynthesis due to the highly energy-intensive CP present in the muscles and the adenosine diphosphate (ADP) formed during the breakdown of ATP with the formation of creatine (K): ADP + + CF → ATP + K. This is instant ATP resynthesis, while the muscle can develop high power, but for a short time - up to 6 s, since the reserves of CF in the muscle are limited.

2. The anaerobic glycolytic energy system provides ATP resynthesis due to the energy of the anaerobic breakdown of glucose to lactic acid. This pathway of ATP resynthesis is fast, but also short-lived (1–2 min), since the accumulation of lactic acid inhibits the activity of glycolytic enzymes. However, lactate, by causing a local vasodilating effect, improves blood flow in the working muscle and the supply of oxygen and nutrients to it.

3. The aerobic energy system provides ATP resynthesis with the help of oxidative phosphorylation of carbohydrates and fatty acids occurring in the mitochondria of muscle cells. This way can provide energy for muscle work for several hours and is the main way to provide energy for the work of skeletal muscles.

Neuromuscular transmission of excitation. We have already shown above that the conduction of excitation in nerve and muscle fibers is carried out with the help of electrical impulses propagating along the surface membrane. The transmission of excitation from the nerve to the muscle is based on a different mechanism. It is carried out as a result of the release of highly active chemical compounds by the nerve endings - mediators of the nerve impulse. In skeletal muscle synapses, such a mediator is acetylcholine (ACh).

In the neuromuscular synapse, there are three main structural elements - presynaptic membrane on the nerve postsynaptic membrane on the muscle, between them - synaptic cleft . The shape of the synapse can be varied. At rest, ACh is contained in the so-called synaptic vesicles inside the end plate of the nerve fiber. The cytoplasm of the fiber with synaptic vesicles floating in it is separated from the synaptic cleft by the presynaptic membrane. When the presynaptic membrane is depolarized, its charge and permeability change, the bubbles come close to the membrane and pour out into the synaptic cleft, the width of which reaches 200-1000 angstroms. The mediator begins to diffuse through the gap to the postsynaptic membrane.

The postsynaptic membrane is not electrogenic, but has a high sensitivity to the mediator due to the presence in it of the so-called cholinergic receptors - biochemical groups that can selectively react with ACh. The latter reaches the postsynaptic membrane in 0.2-0.5 msec. (so-called "synaptic delay") and, interacting with cholinergic receptors, causes a change in the membrane permeability for Na, which leads to depolarization of the postsynaptic membrane and the generation of a depolarization wave on it, which is called excitatory postsynaptic potential, (EPSP), the value of which exceeds the Ek of neighboring, electrogenic sections of the muscle fiber membrane. As a result, an AP (action potential) arises in them, which spreads over the entire surface of the muscle fiber, then causing its contraction, initiating the process of the so-called. electromechanical interface (Kapling). The mediator in the synaptic cleft and on the postsynaptic membrane works for a very short time, as it is destroyed by the enzyme cholinesterase, which prepares the synapse to receive a new portion of the mediator. It has also been shown that part of the unreacted ACh can return to the nerve fiber.

With very frequent stimulation rhythms, postsynaptic potentials can be summed up, since cholinesterase does not have time to completely break down the ACh released in the nerve endings. As a result of this summation, the postsynaptic membrane becomes more and more depolarized. At the same time, neighboring electrogenic sections of the muscle fiber come into a state of depression, similar to that which develops during prolonged action of the direct current cathode. (Verigo's cathodic depression).

Functions and properties of striated muscles.

The striated muscles are the active part of the musculoskeletal system. As a result of the contractile activity of these muscles, the body moves in space, the parts of the body move relative to each other, and the posture is maintained. In addition, during muscular work, heat is generated.

Each muscle fiber has the following properties: excitability , those. the ability to respond to the action of the stimulus by generating AP, conductivity - the ability to conduct excitation along the entire fiber in both directions from the point of irritation, and contractility , i.e. the ability to contract or change its tension when excited. Excitability and conductivity are functions of the surface cell membrane - the sarcolemma, and contractility is a function of the myofibrils located in the sarcoplasm.

Research methods. Under natural conditions, the excitation and contraction of muscles is caused by nerve impulses. In order to excite a muscle in an experiment or in a clinical study, it is subjected to artificial stimulation with an electric current. Direct irritation of the muscle itself is called direct, and irritation of the nerve is called indirect irritation. Due to the fact that the excitability of muscle tissue is less than that of nervous tissue, the application of electrodes directly to the muscle does not yet provide direct irritation - the current, spreading through the muscle tissue, acts primarily on the endings of the motor nerves located in it. Pure direct irritation is obtained only with intracellular irritation or after poisoning of the nerve endings with curare. Registration of muscle contraction is carried out using mechanical devices - myographs, or special sensors. When studying muscles, electron microscopy, recording of biopotentials during intracellular recording, and other subtle techniques are used to study the properties of muscles both in the experiment and in the clinic.

Mechanisms of muscle contraction.

The structure of myofibrils and its changes during contraction. Myofibrils are the contractile apparatus of the muscle fiber. In striated muscle fibers, myofibrils are divided into regularly alternating sections (discs) with different optical properties. Some of these sections are anisotropic, i.e. have double refraction. In ordinary light they look dark, but in polarized light they are transparent in the longitudinal direction and opaque in the transverse direction. Other areas are isotropic, and appear transparent in ordinary light. Anisotropic regions are denoted by the letter BUT, isotropic - I. In the middle of disk A there is a light strip H, and in the middle of disk I there is a dark stripe Z, which is a thin transverse membrane through the pores of which myofibrils pass. Due to the presence of such a support structure, parallel single-valued disks of individual myofibrils within one fiber do not move relative to each other during contraction.

It has been established that each of the myofibrils has a diameter of about 1 micron and consists of an average of 2500 protofibrils, which are elongated molecules polymerized by the protein myosin and actin. Myosin filaments (protofibrils) are twice as thick as actin filaments. Their diameter is approximately 100 angstroms. In the resting state of the muscle fiber, the filaments are located in the myofibril in such a way that the thin long actin filaments enter with their ends into the gaps between the thick and shorter myosin filaments. In such a section, each thick thread is surrounded by 6 thin ones. Due to this, disks I consist only of actin filaments, and disks A also consist of myosin filaments. The light stripe H is a zone free from actin filaments during the dormant period. Membrane Z, passing through the middle of disc I, holds the actin filaments together.

Numerous cross-bridges on myosin are also an important component of the ultramicroscopic structure of myofibrils. In turn, there are so-called active centers on actin filaments, at rest covered, like a sheath, with special proteins - troponin and tropomyosin. Contraction is based on the sliding of actin filaments relative to myosin filaments. Such sliding is caused by the work of the so-called. "chemical gear", ie. periodically occurring cycles of changes in the state of cross bridges and their interaction with active centers on actin. ATP and Ca+ ions play an important role in these processes.

When the muscle fiber contracts, the actin and myosin filaments do not shorten, but begin to slide over each other: the actin filaments move between the myosin filaments, as a result of which the length of the I disks is shortened, and the A disks retain their size, approaching each other. The H strip almost disappears, because the ends of the actin are in contact and even go behind each other.

The role of AP in the occurrence of muscle contraction (the process of electromechanical coupling). In skeletal muscle, under natural conditions, the initiator of muscle contraction is the action potential, which propagates upon excitation along the surface membrane of the muscle fiber.

If the tip of the microelectrode is applied to the surface of the muscle fiber in the area of the Z membrane, then when a very weak electrical stimulus is applied that causes depolarization, the I disks on both sides of the stimulation site will begin to shorten. in this case, the excitation propagates deep into the fiber, along the Z membrane. Irritation of other sections of the membrane does not cause such an effect. From this it follows that the depolarization of the surface membrane in the region of disc I during AP propagation is the trigger of the contractile process.

Further studies showed that an important intermediate link between membrane depolarization and the onset of muscle contraction is the penetration of free CA++ ions into the interfibrillar space. At rest, most of the Ca++ in the muscle fiber is stored in the sarcoplasmic reticulum.

In the mechanism of muscle contraction, a special role is played by that part of the reticulum, which is localized in the region of the Z membrane. triad (T-system), each of which consists of a thin transverse tubule located centrally in the Z membrane region, running across the fiber, and two lateral cisterns of the sarcoplasmic reticulum, in which bound Ca ++ is enclosed. AP propagating along the surface membrane is conducted deep into the fiber along the transverse tubules of the triads. Then the excitation is transferred to the cisternae, depolarizes their membrane and it becomes permeable to CA++.

It has been experimentally established that there is a certain critical concentration of free Ca++ ions, at which the contraction of myofibrils begins. It is equal to 0.2-1.5*10 6 ions per fiber. Increasing the concentration of Ca++ to 5*10 6 already causes the maximum reduction.

The onset of muscle contraction is timed to the first third of the ascending AP knee, when its value reaches approximately 50 mV. It is believed that it is at this depolarization level that the concentration of Ca++ becomes the threshold for the beginning of the interaction between actin and myosin.

The Ca++ release process stops after the end of the AP peak. Nevertheless, the contraction continues to grow until the mechanism that ensures the return of Ca ++ to the reticulum cisterns comes into action. This mechanism is called the "calcium pump". To carry out its work, the energy obtained from the breakdown of ATP is used.

In the interfibrillar space, Ca++ interacts with proteins that close the active centers of actin filaments - troponin and tropomyosin, providing an opportunity for the reaction of myosin cross-bridges and actin filaments.

Thus, the sequence of events leading to contraction and then to relaxation of the muscle fiber is currently drawn as follows:

Irritation - the occurrence of AP - its conduction along the cell membrane and deep into the fiber through the tubules of T-systems - depolarization of the membrane sarcoplasmic reticulum -- release of Ca++ from triads and its diffusion to myofibrils -- interaction of Ca++ with troponin and release of ATP energy -- interaction (sliding) of actin and myosin filaments -- muscle contraction -- decrease in Ca++ concentration in the interfibrillar space due to the work of the Ca-pump - muscle relaxation .

The role of ATP in the mechanism of muscle contraction. In the process of interaction between actin and myosin filaments in the presence of Ca++ ions, an important role is played by the energy-rich compound, ATP. Myosin has the properties of the enzyme ATPase. When ATP is broken down, about 10,000 calories are released. per 1 mol. Under the influence of ATP, the mechanical properties of myosin filaments also change - their extensibility sharply increases. It is believed that the breakdown of ATP is the source of energy necessary for the sliding of threads. Ca++ ions increase the ATP-ase activity of myosin. In addition, the energy of ATP is used to operate the calcium pump in the reticulum. Accordingly, ATP-cleaving enzymes are localized in these membranes, and not only in myosin.

The resynthesis of ATP, which is continuously split during muscle work, is carried out in two main ways. The first is the enzymatic transfer of the phosphate group from creatine phosphate (CP) to ADP. CF is contained in the muscle in much larger quantities than ATP, and ensures its resynthesis within thousandths of a second. However, during prolonged muscle work, CF reserves are depleted, so the second way is important - slow ATP resynthesis associated with glycolysis and oxidative processes. The oxidation of lactic and pyruvic acids formed in the muscle during its contraction is accompanied by the phosphorylation of ADP and creatine, i.e. resynthesis of CP and ATP.

Violation of ATP resynthesis by poisons that suppress glycolysis and oxidative processes leads to the complete disappearance of ATP and CP, as a result of which the calcium pump stops working. The concentration of Ca ++ in the area of myofibrils increases greatly and the muscle enters a state of long-term irreversible shortening - the so-called. contractures.

Heat generation during the contraction process. According to its origin and time of development, heat generation is divided into two phases. The first is many times shorter than the second and is called the initial heat generation. It starts from the moment of excitation of the muscle and continues throughout the entire contraction, including the relaxation phase. The second phase of heat generation occurs within a few minutes after relaxation, and is called delayed, or restorative heat generation. In turn, the initial heat generation can be divided into several parts - activation heat, shortening heat, and relaxation heat. The heat generated in the muscles maintains the temperature of the tissues at a level that ensures the active flow of physical and chemical processes in the body.

Types of abbreviations. Depending on the conditions in which the reduction occurs,

nie, there are two types of it - isotonic and isometric . Isotonic is the contraction of the muscle, in which its fibers are shortened, but the tension remains the same. An example is shortening without load. An isometric contraction is such a contraction in which the muscle cannot shorten (when its ends are fixedly fixed). In this case, the length of the muscle fibers remains unchanged, but their tension increases (lifting an unbearable load).

Natural muscle contractions in the body are never purely isotonic or isometric.

Single cut. Irritation of a muscle or motor nerve innervating it with a single stimulus causes a single muscle contraction. It distinguishes two main phases: the contraction phase and the relaxation phase. The contraction of the muscle fiber begins already during the ascending branch of the AP. The duration of contraction at each point of the muscle fiber is tens of times greater than the duration of AP. Therefore, there comes a moment when the AP has passed along the entire fiber and ended, while the contraction wave has covered the entire fiber and it continues to be shortened. This corresponds to the moment of maximum shortening or tension of the muscle fiber.

The contraction of each individual muscle fiber during single contractions obeys the law " all or nothing". This means that the contraction that occurs both with threshold and supra-threshold stimulation has a maximum amplitude. The magnitude of a single contraction of the entire muscle depends on the strength of the irritation. With threshold stimulation, its contraction is barely noticeable, but with an increase in the strength of irritation it increases, until it reaches a certain height, after which it remains unchanged (maximum contraction). This is due to the fact that the excitability of individual muscle fibers is not the same, and therefore only part of them is excited with weak irritation. At maximum contraction, they are all excited. The speed of the wave of muscle contraction is the same with the speed of propagation of AP.In the biceps muscle of the shoulder, it is 3.5-5.0 m/sec.

Contraction summation and tetanus. If, in an experiment, an individual muscle fiber or the entire muscle is affected by two rapidly following each other strong single stimuli, then the resulting contraction will have a greater amplitude than the maximum single contraction. The contractile effects caused by the first and second irritation seem to add up. This phenomenon is called the summation of contractions. For summation to occur, it is necessary that the interval between stimuli has a certain duration - it must be longer than the refractory period, but shorter than the entire duration of a single contraction, so that the second stimulus acts on the muscle before it has time to relax. In this case, two cases are possible. If the second stimulation arrives when the muscle has already begun to relax, on the myographic curve the top of the second contraction will be separated from the first by a depression. If the second irritation acts when the first contraction has not yet reached its peak, then the second contraction, as it were, merges with the first, forming with it a single summed peak. Both with full and incomplete summation, PDs are not summed up. Such a summed contraction in response to rhythmic stimuli is called tetanus. Depending on the frequency of irritation, it is serrated and smooth.

The reason for the summation of contractions in tetanus lies in the accumulation of Ca ++ ions in the interfibrillar space up to a concentration of 5 * 10 6 mM / l. After reaching this value, further accumulation of Ca++ does not lead to an increase in the tetanus amplitude.

After the termination of tetanic irritation, the fibers do not relax completely at first, and their original length is restored only after some time has passed. This phenomenon is called post-tetanic, or residual contracture. She is connected to it. that it takes more time to remove all Ca ++ from the interfibrillar space, which got there with rhythmic stimuli and did not have time to completely withdraw into the cisterns of the sarcoplasmic reticulum by the work of Ca-pumps.

If, after reaching a smooth tetanus, the frequency of stimulation is increased even more, then the muscle at a certain frequency suddenly begins to relax. This phenomenon is called pessimism. It occurs when each next impulse falls into refractoriness from the previous one.

Motor units. We have considered the general scheme of the phenomena underlying tetanic contraction. In order to get to know in more detail how this process takes place under the conditions of the natural activity of the body, it is necessary to dwell on some features of the innervation of the skeletal muscle by the motor nerve.

Each motor nerve fiber, which is a process of the motor cell of the anterior horns of the spinal cord (alpha motor neuron), branches in the muscle and innervates a whole group of muscle fibers. Such a group is called the motor unit of the muscle. The number of muscle fibers that make up the motor unit varies widely, but their properties are the same (excitability, conductivity, etc.). Due to the fact that the speed of propagation of excitation in the nerve fibers innervating the skeletal muscles is very high, the muscle fibers that make up the motor unit come into a state of excitation almost simultaneously. The electrical activity of the motor unit has the form of a palisade, in which each peak corresponds to the total action potential of many simultaneously excited muscle fibers.

It should be said that the excitability of various skeletal muscle fibers and the motor units consisting of them varies significantly. She is more in the so-called. fast and less in slow fibers. At the same time, the excitability of both is lower than the excitability of the nerve fibers that innervate them. It depends on the fact that in the muscles the difference between E0-E k is greater, and, therefore, the reobase is higher. PD reaches 110-130 mV, its duration is 3-6 ms. The maximum frequency of fast fibers is about 500 per second, most skeletal fibers - 200-250 per second. The duration of AP in slow fibers is about 2 times longer, the duration of the contraction wave is 5 times longer, and the speed of its conduction is 2 times slower. In addition, fast fibers are divided depending on the speed of contraction and lability into phasic and tonic.

Skeletal muscles in most cases are mixed: they consist of both fast and slow fibers. But within one motor unit, all fibers are always the same. Therefore, motor units are divided into fast and slow, phasic and tonic. The mixed type of muscle allows the nerve centers to use the same muscle both to carry out fast, phasic movements and to maintain tonic tension.

There are, however, muscles that are predominantly composed of fast or slow motor units. Such muscles are often also called fast (white) and slow (red). The duration of the contraction wave of the fastest muscle - the internal rectus muscle of the eye - is only 7.5 ms, for the slow soleus - 75 ms. The functional significance of these differences becomes apparent when considering their responses to rhythmic stimuli. To obtain a smooth tetanus of a slow muscle, it is enough to irritate it with a frequency of 13 stimuli per second. in fast muscles, smooth tetanus occurs at a frequency of 50 stimuli per second. In tonic motor units, the duration of contraction for a single stimulus can be up to 1 second.

Summation of motor unit contractions in a whole muscle. Unlike muscle fibers in a motor unit, which fire synchronously in response to an incoming impulse, muscle fibers of different motor units in a whole muscle fire asynchronously. This is explained by the fact that different motor units are innervated by different motor neurons, which send impulses at different frequencies and at different times. Despite this total contraction of the muscle as a whole, under conditions of normal activity, it has a fused character. This is because the neighboring motor unit (or units) always has time to contract before those that are already excited have time to relax. The strength of muscle contraction depends on the number of motor units involved in the reaction at the same time, and on the frequency of excitation of each of them.

Skeletal muscle tone. At rest, outside of work, the muscles in the body are not

completely relaxed, but retain some tension, called tone. The external expression of tone is a certain elasticity of the muscles.

Electrophysiological studies show that the tone is associated with the supply of rare nerve impulses to the muscle, which alternately excite various muscle fibers. These impulses arise in the motor neurons of the spinal cord, the activity of which, in turn, is supported by impulses coming from both higher centers and proprioreceptors (muscle spindles, etc.) located in the muscles themselves. The reflex nature of skeletal muscle tone is evidenced by the fact that transection of the posterior roots, through which sensitive impulses from muscle spindles enter the spinal cord, leads to complete relaxation of the muscle.

Muscle work and strength. The amount of contraction (degree of shortening) of the muscle at a given strength of stimulation depends both on its morphological properties and on the physiological state. Long muscles contract more than short ones. Moderate stretching of the muscle increases its contractile effect, with strong stretching, the contracted muscles relax. If, as a result of prolonged work, muscle fatigue develops, then the magnitude of its contraction falls.

To measure muscle strength, either the maximum load that it is able to lift, or the maximum tension that it can develop under conditions of isometric contraction, is determined. This power can be very great. Thus, it has been established that a dog with its jaw muscles can lift a load exceeding its body weight by 8.3 times.

A single muscle fiber can develop tension up to 100-200 mg. Considering that the total number of muscle fibers in the human body is approximately 15-30 million, they could develop a tension of 20-30 tons if they all pulled in one direction at the same time.

Muscle strength, other things being equal, depends on its cross section. The greater the sum of the cross sections of all its fibers, the greater the load that it is able to lift. This means the so-called. physiological cross section, when the line of section is perpendicular to the muscle fibers, and not to the muscle as a whole. The strength of muscles with oblique fibers is greater than with straight fibers, since its physiological cross section is greater with the same geometric. To compare the strength of different muscles, the maximum load (absolute muscle strength) that the muscle is able to lift is divided by the physiological cross-sectional area (kg / cm2). Thus, the specific absolute strength of the muscle is calculated. For the human gastrocnemius muscle, it is 5.9 kg / cm2, the shoulder flexor - 8.1 kg / cm2, the triceps muscle of the shoulder - 16.8 kg / cm2.

Muscle work is measured by the product of the lifted load by the amount of shortening of the muscle. Between the load that the muscle lifts and the work it performs, there is the following pattern. The external work of a muscle is zero if the muscle contracts without load. As the load increases, the work first increases and then gradually decreases. The muscle performs the greatest work at some average loads. Therefore, the dependence of work and power on the load is called rules (of law) medium loads .

The work of the muscles, in which the movement of the load and the movement of the bones in the joints, is called dynamic. The work of the muscle, in which the muscle fibers develop tension, but almost do not shorten - static. An example is hanging on a pole. Static work is more tedious than dynamic work.

Muscle fatigue. Fatigue is a temporary decrease in working capacity

function of a cell, organ or whole organism, which occurs as a result of work and disappears after rest.

If for a long time an isolated muscle, to which a small load is suspended, is irritated with rhythmic electrical stimuli, then the amplitude of its contractions gradually decreases until it drops to zero. The fatigue curve is recorded. Along with a change in the amplitude of contractions during fatigue, the latent period of contraction increases, the period of muscle relaxation lengthens, and the stimulation threshold increases, i.e. excitability decreases. All these changes do not occur immediately after the start of work, there is a certain period during which there is an increase in the amplitude of contractions and a slight increase in muscle excitability. At the same time, it becomes easily stretchable. In such cases, they say that the muscle is "worked in", i.e. adapts to work in a given rhythm and strength of irritation. After a period of workability, a period of stable performance begins. With further prolonged irritation, fatigue of the muscle fibers occurs.

The decrease in the efficiency of a muscle isolated from the body during its prolonged irritation is due to two main reasons. The first of these is that during contractions, metabolic products accumulate in the muscle (phosphoric acid, which binds Ca ++, lactic acid, etc.), which have a depressing effect on muscle performance. Some of these products, as well as Ca ions, diffuse out of the fibers into the pericellular space and have a depressing effect on the ability of the excitable membrane to generate AP. So, if an isolated muscle placed in a small volume of Ringer's fluid is brought to complete fatigue, then it is enough just to change the solution washing it to restore muscle contractions.

Another reason for the development of fatigue in an isolated muscle is the gradual depletion of energy reserves in it. With prolonged work, the content of glycogen in the muscle decreases sharply, as a result of which the processes of ATP and CP resynthesis, which are necessary for the contraction, are disrupted.

It should be noted that under the natural conditions of the organism's existence, fatigue of the motor apparatus during prolonged work develops in a completely different way than in an experiment with an isolated muscle. This is due not only to the fact that in the body the muscle is continuously supplied with blood, and, therefore, receives the necessary nutrients with it and is released from metabolic products. The main difference is that in the body, excitatory impulses come to the muscle from the nerve. The neuromuscular synapse gets tired much earlier than the muscle fiber, due to the rapid depletion of the accumulated mediator. This causes a blockade of the transmission of excitations from the nerve to the muscle, which prevents the muscle from exhaustion caused by prolonged work. In a whole organism, the nerve centers (nerve-nerve contacts) get tired even earlier during work.

The role of the nervous system in the fatigue of the whole organism is proved by studies of fatigue in hypnosis (kettlebell-basket), the establishment of the influence of "active rest" on fatigue, the role of the sympathetic nervous system (the Orbeli-Ginetsinsky phenomenon), etc.

Ergography is used to study muscle fatigue in humans. The shape of the fatigue curve and the amount of work done vary enormously in different individuals and even in the same subject under different conditions.

Working muscle hypertrophy and inactivity atrophy. Systematic intensive work of the muscle leads to an increase in the mass of muscle tissue. This phenomenon is called working muscle hypertrophy. It is based on an increase in the mass of the protoplasm of muscle fibers and the number of myofibrils contained in them, which leads to an increase in the diameter of each fiber. At the same time, the synthesis of nucleic acids and proteins is activated in the muscle and the content of ATP and CPA, as well as glycogen, increases. As a result, the strength and speed of contraction of the hypertrophied muscle increase.

An increase in the number of myofibrils during hypertrophy is facilitated mainly by static work, which requires a lot of stress (power load). Even short-term exercises carried out daily in an isometric mode are sufficient for an increase in the number of myofibrils. Dynamic muscle work, performed without much effort, does not lead to muscle hypertrophy, but can affect the entire body as a whole, increasing its resistance to adverse factors.

The opposite of working hypertrophy is muscle atrophy from inactivity. It develops in all cases when the muscles somehow lose the ability to do their normal work. This happens, for example, with prolonged immobilization of a limb in a plaster cast, a long stay of the patient in bed, transection of the tendon, etc. With muscle atrophy, the diameter of muscle fibers and the content of contractile proteins, glycogen, ATP and other substances important for contractile activity in them decreases sharply. With the resumption of normal muscle work, atrophy gradually disappears. A special type of muscle atrophy is observed during denervation of the muscle, i.e. after transection of her motor nerve.

Smooth muscles Functions of smooth muscles in different organs.

Smooth muscles in the body are located in the internal organs, blood vessels, and skin. Smooth muscles are capable of relatively slow movements and prolonged tonic contractions.

Relatively slow, often rhythmic contractions of the smooth muscles of the walls of hollow organs (stomach, intestines, ducts of the digestive glands, ureters, bladder, gallbladder, etc.) ensure the movement of contents. Prolonged tonic contractions of smooth muscles are especially pronounced in the sphincters of hollow organs; shrinking them prevents the contents from escaping.

The smooth muscles of the walls of blood vessels, especially arteries and arterioles, are also in a state of constant tonic contraction. The tone of the muscle layer of the walls of the arteries regulates the size of their lumen and thus the level of blood pressure and blood supply to the organs. The tone and motor function of smooth muscles is regulated by impulses coming through the autonomic nerves, humoral influences.

Physiological features of smooth muscles. An important property of smooth muscle is its large plastic , those. the ability to maintain the length given by stretching without changing the stress. Skeletal muscle, on the other hand, shortens immediately after the load is removed. A smooth muscle remains stretched until, under the influence of some kind of irritation, its active contraction occurs. The property of plasticity is of great importance for the normal activity of hollow organs - thanks to it, the pressure inside a hollow organ changes relatively little with different degrees of its filling.

There are different types of smooth muscles. In the walls of most hollow organs there are muscle fibers 50–200 microns long and 4–8 microns in diameter, which are very closely adjacent to each other, and therefore, when viewed under a microscope, it seems that they are morphologically one. Electron microscopic examination shows, however, that they are separated from each other by intercellular gaps, the width of which can be equal to 600-1500 angstroms. Despite this, smooth muscle functions as a single entity. This is expressed in the fact that AP and slow waves of depolarization propagate freely from one fiber to another.

In some smooth muscles, for example, in the ciliary muscle of the eye, or the muscles of the iris, the fibers are located separately, and each has its own innervation. In most smooth muscles, motor nerve fibers are located on only a small number of fibers.

The resting potential of smooth muscle fibers with automaticity exhibits constant small fluctuations. Its value at intracellular assignment is 30-70 mV. The resting potential of smooth muscle fibers that do not have automaticity is stable and equal to 60-70 mV. In both cases, its value is less than the resting potential of the skeletal muscle. This is due to the fact that the membrane of smooth muscle fibers at rest is characterized by a relatively high permeability to Na ions. Action potentials in smooth muscle are also somewhat lower than in skeletal muscle. The excess over the resting potential is no more than 10-20 mV.

The ionic mechanism of AP occurrence in smooth muscles is somewhat different from that in skeletal muscles. It has been established that the regenerative depolarization of the membrane, which underlies the action potential in a number of smooth muscles, is associated with an increase in the permeability of the membrane for Ca++ ions, rather than Na+.

Many smooth muscles are characterized by spontaneous, automatic activity. It is characterized by a slow decrease in the resting membrane potential, which, when a certain level is reached, is accompanied by the onset of AP.

Conduction of excitation along smooth muscle. In nerve and skeletal muscle fibers, excitation propagates through local electric currents that arise between the depolarized and neighboring resting sections of the cell membrane. The same mechanism is characteristic of smooth muscles. However, unlike in skeletal muscle, in smooth muscle an action potential originating in one fiber can propagate to adjacent fibers. This is due to the fact that in the membrane of smooth muscle cells in the area of contacts with neighboring ones there are areas of relatively low resistance through which the current loops that have arisen in one fiber easily pass to the neighboring ones, causing depolarization of their membranes. In this respect, smooth muscle is similar to cardiac muscle. The only difference is that in the heart, the entire muscle is excited from one cell, while in smooth muscles, AP that has arisen in one area propagates only a certain distance from it, which depends on the strength of the applied stimulus.

Another essential feature of smooth muscles is that propagating AP occurs downward only if the applied stimulus simultaneously excites a certain minimum number of muscle cells. This "critical zone" has a diameter of about 100 microns, which corresponds to 20-30 parallel cells. The rate of excitation conduction in various smooth muscles ranges from 2 to 15 cm/sec. those. much less than in skeletal muscle.

As well as in skeletal muscles, in smooth action potentials they have a starting value for the start of the contractile process. The connection between excitation and contraction is also carried out here with the help of Ca ++. However, in smooth muscle fibers, the sarcoplasmic reticulum is poorly expressed; therefore, the leading role in the mechanism of contraction is assigned to those Ca ++ ions that penetrate into the muscle fiber during AP generation.

With a large force of a single irritation, smooth muscle contraction may occur. The latent period of its contraction is much longer than the skeletal period, reaching 0.25-1 sec. The duration of the contraction itself is also large - up to 1 minute. Relaxation is especially slow after contraction. The contraction wave propagates through the smooth muscles at the same speed as the excitation wave (2-15 cm/sec). But this slowness of contractile activity is combined with a great force of smooth muscle contraction. So, the muscles of the stomach of birds are capable of lifting 2 kg per 1 sq. mm. its cross section.

Due to the slowness of contraction, smooth muscle, even with rare rhythmic stimulation (10-12 per minute), easily passes into a long-term state of persistent contraction, resembling tetanus of skeletal muscles. However, the energy costs of such a reduction are very low.

The ability to automate smooth muscles is inherent in their muscle fibers and is regulated by nerve elements that are located in the walls of smooth muscle organs. The myogenic nature of automaticity has been proven by experiments on strips of muscles of the intestinal wall, freed from nerve elements. Smooth muscle responds to all external influences by changing the frequency of spontaneous rhythm, resulting in contraction or relaxation of the muscle. The effect of irritation of the smooth muscles of the intestine depends on the ratio between the frequency of stimulation and the natural frequency of spontaneous rhythm: with a low tone - rare spontaneous AP - the applied irritation increases the tone, with a high tone, relaxation occurs in response to irritation, since an excessive increase in impulses leads to the fact that each next impulse falls into the phase of refractoriness from the previous one.

Smooth muscle irritants. One of the important physiologically adequate stimuli of smooth muscles is their rapid and strong stretching. It causes depolarization of the muscle fiber membrane and the occurrence of propagating AP. As a result, the muscle contracts. A characteristic feature of smooth muscles is their high sensitivity to certain chemical stimuli, in particular, to acetylcholine, norepinephrine, adrenaline, histamine, serotonin, prostaglandins. The effects caused by the same chemical agent in different muscles and in their different states may be different. So, ACh excites the smooth muscles of most organs, but inhibits the muscles of blood vessels. Adrenaline relaxes the non-pregnant uterus but contracts the pregnant one. These differences are due to the fact that these agents react on the membrane with different chemical receptors (cholinergic receptors, alpha and beta adrenoreceptors), and as a result, change the ion permeability and membrane potential of smooth muscle cells in different ways. In cases where the irritating agent causes membrane depolarization, excitation occurs, and, conversely, membrane hyperpolarization under the influence of a chemical agent leads to inhibition of activity and relaxation of smooth muscle.

A. The system of sarcoplasmic tubules of myocytes (muscle fibers)

Stimulation of muscle fibers

Proximity release results in an end plate current that propagates electrotonically and activates fast, voltage-gated Na+ channels in the sarcolemma. This leads to the appearance of (PD), which is carried out at a speed of 2 m/s along the sarcolemma of the entire muscle fiber and quickly penetrates deep into the fiber along the T-system (A).

Genetic defects in the structure of sodium channels slow down their deactivation, which leads to increased excitability with an increase in the duration of contraction and delayed relaxation of the skeletal muscle (myotonia). An increase in muscle activity is accompanied by a massive release of potassium ions from the fiber. This leads to hyperkalemia, whereby the muscle reaches values at which sodium channels can no longer be activated, and the muscle is temporarily paralyzed: familial hylerkalemic periodic paralysis.

B. Ca 2+ as a mediator between electrical stimulation and contraction

The transition from excitation to is called (B). In skeletal muscle, this process begins with an action potential that excites voltage-dependent dihydropyridine receptors (DHPRs) in the sarcolemma near the triads. These receptors are arranged in rows, and opposite them in the adjacent membrane of the sarcoplasmic reticulum are rows of Ca 2+ channels called ryanodine receptors (RYR; in skeletal muscle, type 1 ryanodine receptor, abbreviated RYR1). Every second RYR1 is associated with DHPR (B2). RYR1s open when they mechanically “feel” a change in DHPR conformation in response to an action potential. In the myocardium, each DHPR is part of a voltage-dependent Ca2+ channel in the sarcolemma that opens in response to an action potential. Small amounts of extracellular Ca 2+ enter the cell through this channel, thereby leading to the opening of the myocardial channel RYR2 (the so-called Ca 2+ inducing effect, or "Ca 2+ flash", BZ). The Ca 2+ ions stored in the SR are released through the open RYR1 or RYR2 into the cytoplasm, increasing the cytoplasmic Ca 2+ concentration to over 1 µmol/L compared to a resting concentration of -0.01 µmol/L (B1). In skeletal muscle, DHPR stimulation at one site is sufficient to trigger the “friendly” opening of the entire RYR1 group. Thus, the reliability of the pulse conduction is increased. An increased concentration of Ca 2+ in the cytoplasm saturates the Ca 2+ -binding sites of troponin C, canceling the inhibitory effect of tropomyosin on filament gliding (G), which prevents strong (high-affinity) binding of actin and myosin II.

In patients with RYR1 genetic defects, general anesthesia can lead to a massive calcium surge, which causes violent muscle contractions accompanied by a rapid and life-threatening increase in body temperature: malignant hyperthermia (=fulminant hyperpyrexia).

B. Sliding filaments

ATP molecules are essential for filament glide and therefore for muscle contraction. Due to their ATPase activity, myosin heads act as motors (motor proteins) for this process. The myosin-ll and actin filaments in the sarcomere are organized in such a way that they can slide over each other. Myosin heads connect with actin filaments at a special angle, forming the so-called transverse bridges (B1). Due to conformational changes in the region of the nucleotide-binding site of myosin-ll, the spatial dimensions of which increase with the coordinated movement of the neck region, the myosin head tilts, displacing thin filaments by a total of 4–12 nm (working cycle) in two successive “steps”. The second myosin head may also act on the adjacent actin filament, causing it to contract. The head then detaches and "stretches" in preparation for the next "stroke" when it binds to actin again (B3).

Kinesin, another motor protein, moves independently along the microtubule by "stepping" its two heads (8nm per cycle) like a tug of war. In this case, 50% of the cycle is "working time" (efficiency 0.5). In skeletal muscle, between two successive interactions with actin, myosin-ll itself "jumps" 36 nm (or a multiple of 36 nm, such as a rapid contraction of 396 nm or more) to reach the next (or 11th) a conveniently located actin-binding site (B3, jump from a to b). At the same time, other myosin heads operating on this actin filament must make at least 10 to 100 strokes of approximately 4 nm each. The efficiency of the myosin-ll head is thus 0.1 to 0.01. This "division of labor" between the myosin heads ensures that some proportion of the myosin heads is always ready to make a rapid contraction.

As the filaments slide, the Z-discs approach each other, and the areas of superposition of thin and thick ones become wider, but their total length remains unchanged. This leads to a shortening of the 1-band and the H-zone. When the ends of the thick filaments “push” over the Z-disk, the maximum shortening of the muscle occurs and the ends of the thin filaments overlap. Shortening of the sarcomere thus occurs at both ends of the myosin bundles, but in opposite directions.

D. Duty cycle of sliding filaments

The mechanism of muscle contraction

Each of the two heads of myosin-ll (M) molecules binds one ATP molecule in the nucleotide-binding site with the help of Mg2+ ions. The resulting M-ATP complex is located at an angle of approximately 45° to the rest of the molecule (G4). In this state, myosin has very little affinity for actin. Due to the effect of an increased Ca 2+ concentration in the cytoplasm on the troponin-tropomyosin complex, actin (A) activates myosin ATPase, which leads to ATP hydrolysis (ADP + Pn) and the formation of the actin-myosin-ADP-Pn (G1) complex. After this, the heads of myosin-ll straighten again - the result of this conformational change is that the association constant of actin with myosin increases by four orders of magnitude (B1, G1). Fn (inorganic phosphate) is separated from the complex, which causes the myosin head to deviate by 40° (G2a). This causes the actin and myosin filaments to slide relative to each other (the first phase of the working cycle). The subsequent release of ADP induces the second phase of skeletal muscle contraction, which unequivocally ends with the final position of the myosin heads (G2b). The remaining actin-myosin complex (rigid complex) is stable and can be converted in the presence of ATP into a new complex, where the myosin heads are weakly bound to ATP [the "softening" effect of ATP] G4). Greater resting muscle mobility is important for processes such as cardiac filling or relaxation of the extensor muscle during rapid flexion. If the concentration of Ca 2+ >10-6 mol/l remains in the cytoplasm, cycles I and G4 begin anew. It basically depends on whether the next action potential arrives. To ensure smooth contraction, only a fraction of the myosin heads that pull on the myosin filament are "busy" at a time (low efficiency).

Ca 2+ ions released from the sarcoplasmic reticulum (SR) are continuously pumped back by active transport by Ca 2+ -ATPase, also called SERCA . Thus, if RYR-mediated Ca 2+ release from the sarcoplasmic reticulum is interrupted, then the Ca 2+ concentration in the cytoplasm falls below 10-6 mol/l and filament glide stops (resting state, D, upper left corner).

Parvalbumin, a protein present in the cytoplasm (F-fibers), accelerates muscle relaxation after a short phase of muscle contraction by binding Ca 2+ from the cytoplasm in exchange for Mg 2+ . The affinity of parvalbumin for Ca 2+ is higher than that of troponin, but lower than that of Ca 2+ -ATPase of the sarcoplasmic reticulum. Thus, parvalbumin acts as a "slow" Ca 2+ buffer.

The course of the filament sliding cycle, as described above, mainly refers to isotonic contraction, i.e., contraction during which shortening of the skeletal muscle occurs. During a strictly isometric contraction, when muscle tension increases but muscle length remains unchanged, deflection of the myosin heads and mutual sliding of the filaments cannot occur. Instead, in isometric contraction, force is achieved by deforming the myosin heads (HAs).

The muscle fibers of a dead body do not produce ATP. This means that after death, Ca 2+ is no longer pumped back into the SR and the ATP reserves needed to break down the stable actin-myosin complex are soon depleted. This results in rigor mortis (rigor mortis), which resolves only after the decomposition of actin and myosin in the muscle fiber.

Skeletal muscle mechanics

A. Muscle Strength with Increasing and Decreasing Stimulation Rate

Action potentials generated in the muscle fiber increase the intracellular concentration of Ca 2+ , [Ca 2+ ] intracl., initiating contraction (skeletal muscle; myocardium). In skeletal muscles, the regulation of contraction force is achieved by the participation of a different number of motor units and a change in the frequency of the action potential. A single stimulus, if it is above the threshold level, always leads to the maximum release of Ca 2+ and, thus, to the most intense single contraction (the "all or nothing" response). However, this single stimulus does not induce maximum shortening of the muscle fiber because it is too short to keep the sliding filaments in motion until the final position is reached. Muscle shortening continues only if the second stimulus arrives before the muscle is completely relaxed after the first stimulus. This repetition of the stimulus leads to an increasing mechanical summation, or superposition, of individual beats (A). If the frequency of stimulation becomes so high that the muscle can no longer relax between stimuli, then there is a long maximum contraction of motor units, or tetanus (A). This happens, for example, at 20 Hz in slow twitch muscles, and at 60-100 Hz in fast twitch muscles. Muscle strength during tetanus can be four times greater than during a single skeletal muscle contraction. Ca 2+ concentration somewhat decreases between summing stimuli, and remains high during tetanus.

Rigor rigor, like contracture, is characterized by persistent shortening of the muscles. This state must be distinguished from tetanus. The contracture is not caused by an action potential, but by a persistent local depolarization, for example, due to an increased intracellular concentration of K + (K + -contracture) or an induced release of Ca 2+ , for example, in response to caffeine. The contraction of the so-called isotonic fibers (special fibers of the external muscles of the eye and muscle spindles; p. 326) is also one of the forms of contracture. Isotonic fibers do not respond to stimuli according to the "all or nothing" law, but contract in proportion to the amount of depolarization. The degree of contraction of isotonic fibers is regulated by a change in the concentration of Ca 2+ in the cytoplasm (not by an action potential!).

Conversely, overall muscle tone (reflex tone), or sustained resting skeletal muscle tension, refers to the development of a normal action potential in a single motor unit. Single contractions cannot be registered because the motor units work asynchronously. For example, the pelvic muscles (supporting posture) with apparent rest are in involuntary tension. The tone of the resting muscle is regulated by reflexes and increases with increasing attention.

Types of abbreviations

B. Types of abbreviations

There are different types of muscle contractions. During isometric contraction, muscle strength (tension) changes, while the length of the muscle remains constant. (In the heart muscle, this type is represented by isovolumetric (isovolume) contraction, because the length of the muscle determines the volume of the atria and ventricles.) During isotonic contraction, the length of the muscle changes under the influence of constant muscle force. (In the heart muscle, this type is represented by isobaric contraction (at constant pressure) - muscle strength determines the pressure in the atrium or ventricle.) In auxotonic contraction, muscle length and strength change simultaneously. Isotonic or auxotonic contraction, which is formed on the basis of isometric, is called contraction with afterload.

Muscle extensibility

C. Isometric muscle strength at different sarcomere lengths

Resting muscle containing ATP can be stretched as if it were rubber. The force required to initiate muscle relaxation (R, E, resting force) is very small, but increases exponentially in the case of an elastic muscle (see rest curve, D). Muscle resistance to stretch, which keeps the sliding filaments in the sarcomere from separating, depends to some extent on fascia (fibrous tissue). The main factor, however, is a giant filamentous elastic molecule called titin (or connectin; 1000 nm long, weighing 3 to 3.7 MDa) that is included in the sarcomere (6 titin molecules per myosin filament). In the A band region of each sarcomere, titin is located near the myosin filament and helps to keep it in the center of the sarcomere. The titin molecules in the region of band I are flexible and function as "elastic bands" that counteract the passive contraction of the muscle and influence the rate of its shortening.

D. Active and passive components of muscle strength

The extensibility of the titin molecule (titin can stretch up to about ten times its original length in skeletal muscle and slightly less in cardiac muscle) is determined by the frequent repetition of the PEVK (proline-glutamate-valine-lysine) sequence. When the muscle is very strongly stretched, which is represented by the steepest section of the rest curve (D), elements of the globular chain, called immunoglobulin C2 domains, also unfold. The faster the muscle contracts, the more unexpected and abrupt the action of this "shock absorber" will be.

E. Length-Force Curves for Skeletal and Cardiac Muscles

Length (L) and strength (F), or "tension", muscles are closely related (B, D). The total strength of a muscle is the sum of its active strength and its tension at rest, as described above. Since the active force is determined by the magnitude of all potential actin-myosin interactions, it varies in accordance with the initial length of the sarcomere (C, D). Skeletal muscle can develop maximum active (isometric) force (F0) from its resting length (Lmax; sarcomere length approximately 2 to 2.2 µm; B). When sarcomeres shorten, (L< Lmax), часть тонких филаментов перекрывается - развиваемая сила меньше Fq (В). При L -0,7 /тах (длина саркомера 1,65 мкм) толстые филаменты контактируют с Z-диском - F еще меньше. Кроме того, способность предварительно растянутой мышцы }