Let's consider what ideas about the mechanism of alternating muscle contraction and relaxation boil down to. It is currently accepted that the biochemical cycle of muscle contraction consists of 5 stages (Fig. 20.8):

1) the myosin “head” can hydrolyze to and H 3 PO 4 (P i), but does not ensure the release of products. Therefore, this process is more stoichiometric than catalytic in nature (see Fig. 20.8, a);

According to modern concepts, in resting muscle (in myofibrils and interfibrillar space) Ca 2+ is maintained below a threshold value as a result of their binding by structures (tubules and vesicles) of the sarcoplasmic reticulum and the so-called T-system with the participation of a special Ca 2+ -binding agent. called calsequestrin, which is part of these structures.

The possibility of a living muscle remaining in a relaxed state if it contains a sufficiently high muscle is explained by a decrease, as a result of the action of the calcium pump, Ca 2+ in the environment surrounding the myofibrils, below the limit at which the manifestation of ATPase and contractility of the actomyosin structures of the fiber are still possible. Rapid contraction of a muscle fiber when it is irritated by a nerve (or electric shock) is the result of a sudden change in permeability and, as a consequence, the release of a certain amount of Ca 2+ from the cisterns and tubules of the sarcoplasmic reticulum and the T-system into the sarcoplasm.

As noted, the “sensitivity” of the actomyosin system to Ca 2+ (i.e., loss of the ability to cleave and contract in the presence of Ca 2+ when Ca 2+ decreases to 10 –7 M) is due to the presence in the contractile system (on the filaments of F-actin)

Muscle contraction is a complex mechano-chemical process during which the chemical energy of the hydrolytic breakdown of ATP is converted into mechanical work performed by the muscle.

At present, this mechanism has not yet been fully disclosed. But the following is certain:

1. The source of energy necessary for muscle work is ATP;

2. ATP hydrolysis, accompanied by the release of energy, is catalyzed by myosin, which, as already noted, has enzymatic activity;

3. The trigger mechanism for muscle contraction is an increase in the concentration of Ca 2+ ions in the sarcoplasm of myocytes, caused by a motor nerve impulse;

4. During muscle contraction, cross bridges or adhesions arise between thick and thin filaments of myofibrils;

5. During muscle contraction, thin filaments slide along thick filaments, which leads to shortening of myofibrils and the entire muscle fiber as a whole.

There are many hypotheses trying to explain the molecular mechanism of muscle contraction. The most justified at present is hypothesis « rowing boat » or « rowing hypothesis » H. Huxley. In a simplified form, its essence is as follows.

In a muscle at rest, thick and thin filaments of myofibrils are not connected to each other, since the binding sites on actin molecules are covered by tropomyosin molecules.

Muscle contraction occurs under the influence of a motor nerve impulse, which is a wave of increased membrane permeability propagating along the nerve fiber. This wave of increased permeability is transmitted through the neuromuscular junction to the T-system of the sarcoplasmic reticulum and ultimately reaches cisterns containing high concentrations of calcium ions. As a result of a significant increase in the permeability of the tank walls ( this is also a membrane!) calcium ions leave the tanks and their concentration in the sarcoplasm is very a short time (about 3 ms) increases approximately 1000 times. Calcium ions, being in high concentration, attach to the protein of thin filaments - troponin and change its spatial shape ( conformation). A change in the conformation of troponin, in turn, leads to the fact that tropomyosin molecules are displaced along the groove of fibrillar actin, which forms the basis of thin filaments, and release that portion of actin molecules that is intended for binding to myosin heads. As a result, between myosin and actin ( those. between thick and thin threads) a transverse bridge appears, located at an angle of 90 º . Since thick and thin filaments contain a large number of myosin and actin molecules (about 300 each). then a fairly large number of transverse bridges or adhesions are formed between the muscle threads. In the electron micrograph ( rice. 15) it is clearly visible that between the thick and thin threads there are a large number of transversely located bridges.

Rice. 15. Electron micrograph of longitudinal cut

myofibril area(magnification 300,000 times)(L. Streiner, 1985)

The formation of a bond between actin and myosin is accompanied by an increase in the ATPase activity of the latter ( those. actin acts as an allosteric enzyme activator). resulting in ATP hydrolysis:

Chapter 1. EXCITABLE TISSUE

PHYSIOLOGY OF MUSCLE TISSUE

Skeletal muscles

Mechanism of muscle contraction

Skeletal muscle is a complex system that converts chemical energy into mechanical work and heat. Currently, the molecular mechanisms of this transformation are well studied.

Structural organization of muscle fiber. Muscle fiber is a multinuclear structure surrounded by a membrane and containing a specialized contractile apparatus - myofibrils. In addition, the most important components of muscle fiber are mitochondria, a system of longitudinal tubes - the sarcoplasmic reticulum (reticulum) and a system of transverse tubes - the T-system. The functional unit of the contractile apparatus of a muscle cell is the sarcomere (Fig. 2.20, A); The myofibril consists of sarcomeres. Sarcomeres are separated from each other by Z-plates. Sarcomeres in the myofibril are arranged sequentially, so contraction of the sarcomeres causes contraction of the myofibril and overall shortening of the muscle fiber.

Studying the structure of muscle fibers in a light microscope revealed their transverse striations. Electron microscopic studies have shown that cross-striations are due to the special organization of the contractile proteins of myofibrils - actin (molecular weight 42,000) and myosin (molecular weight about 500,000). Actin filaments are represented by a double filament twisted into a double helix with a pitch of about 36.5 nm. These filaments are 1 µm long and 6-8 nm in diameter, the number of which reaches about 2000, and are attached at one end to the Z-plate. Filament-like molecules of the protein tropomyosin are located in the longitudinal grooves of the actin helix. In increments of 40 nm, a molecule of another protein, troponin, is attached to the tropomyosin molecule. Troponin and tropomyosin play an important role in the mechanisms of interaction between actin and myosin. In the middle of the sarcomere, between the actin filaments, there are thick myosin filaments about 1.6 µm long. In a polarizing microscope, this area is visible as a strip of dark color (due to birefringence) - an anisotropic A-disk. A lighter stripe H is visible in its center. At rest, there are no actin filaments in it. On both sides of the A-disc, light isotropic stripes are visible - I-discs formed by actin filaments. At rest, the actin and myosin filaments overlap each other slightly so that the total length of the sarcomere is about 2.5 μm. Electron microscopy revealed an M-line in the center of the H-band, a structure that holds myosin filaments. On a cross section of a muscle fiber, you can see the hexagonal organization of the myofilament: each myosin thread is surrounded by six actin threads (Fig. 2.20, B).

Electron microscopy shows that on the sides of the myosin filament there are protrusions called cross bridges. They are oriented relative to the axis of the myosin filament at an angle of 120°. According to modern concepts, the transverse bridge consists of a head and a neck. The head acquires pronounced ATPase activity upon binding to actin. The neck has elastic properties and is a hinged joint, so the head of the cross bridge can rotate around its axis.

The use of microelectrode technology in combination with interference microscopy has made it possible to establish that applying electrical stimulation to the Z-plate region leads to a contraction of the sarcomere, while the size of the A disk zone does not change, and the size of the H and I stripes decreases. These observations indicated that the length of myosin filaments does not change. Similar results were obtained when the muscle was stretched - the intrinsic length of actin and myosin filaments did not change. As a result of these experiments, it became clear that the area of ​​mutual overlap of actin and myosin filaments changed. These facts allowed N. Huxley and A. Huxley to independently propose the theory of thread sliding to explain the mechanism of muscle contraction. According to this theory, during contraction, the size of the sarcomere decreases due to the active movement of thin actin filaments relative to thick myosin filaments. Currently, many details of this mechanism have been clarified and the theory has received experimental confirmation.

The mechanism of muscle contraction. During the process of muscle fiber contraction, the following transformations occur in it:

A. Electrochemical conversion:

2. Distribution of PD through the T-system.

3. Electrical stimulation of the contact zone of the T-system and the sarcoplasmic reticulum, activation of enzymes, formation of inositol triphosphate, increase in the intracellular concentration of Ca2+ ions.

B. Chemomechanical transformation:

4. Interaction of Ca2+ ions with troponin, release of active centers on actin filaments.

5. Interaction of the myosin head with actin, rotation of the head and development of elastic traction.

6. Sliding of actin and myosin filaments relative to each other, reducing the size of the sarcomere, developing tension or shortening of the muscle fiber.

The transfer of excitation from the motor neuron to the muscle fiber occurs with the help of the mediator acetylcholine (ACh). The interaction of ACh with the endplate cholinergic receptor leads to activation of ACh-sensitive channels and the appearance of an endplate potential, which can reach 60 mV. In this case, the area of ​​the end plate becomes a source of irritating current for the muscle fiber membrane and in areas of the cell membrane adjacent to the end plate, an PD occurs, which spreads in both directions at a speed of approximately 3-5 m/s at a temperature of 36 oC. Thus, the generation of PD is the first stage of muscle contraction.

The second stage is the propagation of PD into the muscle fiber through the transverse system of tubules, which serves as a link between the surface membrane and the contractile apparatus of the muscle fiber. The T-system is in close contact with the terminal cisterns of the sarcoplasmic reticulum of two neighboring sarcomeres. Electrical stimulation of the contact site leads to the activation of enzymes located at the contact site and the formation of inositol triphosphate. Inositol triphosphate activates calcium channels in the membranes of the terminal cisterns, which leads to the release of Ca2+ ions from the cisterns and an increase in the intracellular Ca2+ concentration from 107 to 105 M. The set of processes leading to an increase in the intracellular Ca2+ concentration constitutes the essence of the third stage of muscle contraction. Thus, at the first stages, the electrical signal of the AP is converted into a chemical one - an increase in the intracellular concentration of Ca2+, i.e., an electrochemical transformation.

With an increase in the intracellular concentration of Ca2+ ions, tropomyosin shifts into the groove between the actin filaments, and areas on the actin filaments open with which myosin cross bridges can interact. This displacement of tropomyosin is due to a change in the conformation of the troponin protein molecule upon Ca2+ binding. Consequently, the participation of Ca2+ ions in the mechanism of interaction between actin and myosin is mediated through troponin and tropomyosin.

The essential role of calcium in the mechanism of muscle contraction was proven in experiments using the protein aequorin, which emits light when interacting with calcium. After injection of aequorin, the muscle fiber was electrically stimulated and simultaneously measured muscle tension in isometric mode and aequorin luminescence. Both curves were completely correlated with each other (Fig. 2.21). Thus, the fourth stage of electromechanical coupling is the interaction of calcium with troponin.

The next, fifth, stage of electromechanical coupling is the attachment of the head of the cross bridge to the actin filament to the first of several sequentially located stable centers. In this case, the myosin head rotates around its axis, since it has several active centers that sequentially interact with the corresponding centers on the actin filament. Rotation of the head leads to an increase in the elastic traction of the neck of the cross bridge and an increase in tension. At each specific moment during the development of contraction, one part of the heads of the cross bridges is in connection with the actin filament, the other is free, i.e., there is a sequence of their interaction with the actin filament. This ensures a smooth reduction process. At the fourth and fifth stages, a chemomechanical transformation occurs.

Read also: When does parental leave for children under 3 years end?

The sequential reaction of connection and separation of the heads of the cross bridges with the actin filament leads to the sliding of thin and thick filaments relative to each other and a decrease in the size of the sarcomere and the total length of the muscle, which is the sixth stage. The totality of the described processes constitutes the essence of the theory of thread sliding

It was initially believed that Ca2+ ions served as a cofactor for the ATPase activity of myosin. Further research refuted this assumption. In resting muscle, actin and myosin have virtually no ATPase activity. The attachment of the myosin head to actin causes the head to acquire ATPase activity.

Hydrolysis of ATP in the ATPase center of the myosin head is accompanied by a change in the conformation of the latter and its transfer to a new, high-energy state. Reattachment of the myosin head to a new center on the actin filament again leads to rotation of the head, which is provided by the energy stored in it. In each cycle of connection and separation of the myosin head with actin, one ATP molecule is cleaved per bridge. The speed of rotation is determined by the rate of ATP breakdown. It is clear that fast phasic fibers consume significantly more ATP per unit time and retain less chemical energy during tonic exercise than slow fibers. Thus, in the process of chemomechanical transformation, ATP provides the separation of the myosin head and the actin filament and provides energy for further interaction of the myosin head with another part of the actin filament. These reactions are possible at calcium concentrations above 106M.

The described mechanisms of muscle fiber shortening suggest that relaxation first requires a decrease in the concentration of Ca2+ ions. It has been experimentally proven that the sarcoplasmic reticulum has a special mechanism - a calcium pump, which actively returns calcium to the tanks. Activation of the calcium pump is carried out by inorganic phosphate, which is formed during the hydrolysis of ATP, and the energy supply for the operation of the calcium pump is also due to the energy generated during the hydrolysis of ATP. Thus, ATP is the second most important factor, absolutely necessary for the relaxation process. For some time after death, the muscles remain soft due to the cessation of the tonic influence of motor neurons (see Chapter 4). The ATP concentration then decreases below critical level and the possibility of disconnection of the myosin head from the actin filament disappears. The phenomenon of rigor mortis occurs with pronounced rigidity skeletal muscles.

Mechanism of muscle contraction

All muscles of the body are divided into smooth and striated. Striated muscles are divided into two types: skeletal muscles and myocardium.

The structure of muscle fiber

The muscle cell membrane, called the sarcolemma, is electrically excitable and capable of conducting action potentials. These processes in muscle cells occur according to the same principle as in nerve cells. The resting potential of a muscle fiber is approximately -90 mV, that is, lower than that of a nerve fiber (-70 mV); the critical depolarization, upon reaching which an action potential occurs, is the same as that of a nerve fiber. Hence: the excitability of the muscle fiber is somewhat lower than the excitability of the nerve fiber, since the muscle cell needs to be depolarized by a greater amount.

The muscle fiber's response to stimulation is reduction. which is performed by the contractile apparatus of the cell - myofibrils. They are cords consisting of two types of threads: thick - myosin. and thin - actin. Thick filaments (15 nm in diameter and 1.5 µm in length) contain only one protein - myosin. Thin filaments (7 nm in diameter and 1 µm in length) contain three types of proteins: actin, tropomyosin and troponin.

Actin is a long protein thread that consists of individual globular proteins linked together in such a way that the entire structure is an elongated chain. Molecules of globular actin (G-actin) have lateral and terminal binding centers with other similar molecules. As a result, they come together in such a way that they form a structure that is often compared to two strands of beads joined together. The ribbon formed from G-actin molecules is twisted into a spiral. This structure is called fibrillar actin (F-actin). The helix pitch (turn length) is 38 nm; for each turn of the helix there are 7 pairs of G-actin. The polymerization of G-actin, that is, the formation of F-actin, occurs due to the energy of ATP, and, conversely, when F-actin is destroyed, energy is released.

Fig.1. Association of individual G-actin globules into F-actin

The protein tropomyosin is located along the spiral grooves of actin filaments. Each tropomyosin filament, 41 nm long, consists of two identical α-chains twisted together into a spiral with a turn length of 7 nm. Along one turn of F-actin there are two tropomyosin molecules. Each tropomyosin molecule connects, slightly overlapping, to the next, resulting in a tropomyosin filament extending continuously along actin.

Fig.2. The structure of a thin filament of myofibril

In striated muscle cells, the thin filaments, in addition to actin and tropomyosin, also contain the protein troponin. This globular protein has a complex structure. It consists of three subunits, each of which performs a different function during the contraction process.

Thick thread consists of a large number of molecules myosin. collected in a bun. Each myosin molecule, 155 nm long and 2 nm in diameter, consists of six polypeptide threads: two long and four short. The long chains are twisted together into a spiral with a pitch of 7.5 nm and form the fibrillar part of the myosin molecule. At one end of the molecule, these chains unwind and form a forked end. Each of these ends forms a complex with two short chains, that is, there are two heads on each molecule. This is the globular part of the myosin molecule.

Fig.3. The structure of the myosin molecule.

Myosin has two fragments: light meromyosin (LMM) and heavy meromyosin (HMM), between them there is a hinge. TMM consists of two subfragments: S 1 and S 2 . The LMM and subfragment S 2 are embedded in a bundle of threads, and subfragment S 1 protrudes above the surface. This protruding end (myosin head) is able to bind to the active site on the actin filament and change the angle of inclination to the myosin filament bundle. The combination of individual myosin molecules into a bundle occurs due to electrostatic interactions between the LMMs. The central part of the thread has no heads. The entire complex of myosin molecules extends over 1.5 µm. It is one of the largest biological molecular structures known in nature.

When examining a longitudinal section of striated muscle through a polarizing microscope, light and dark areas are visible. Dark areas (disks) are anisotropic: in polarized light they appear transparent in the longitudinal direction and opaque in the transverse direction, designated by the letter A. Light areas are isotropic and designated by the letter I. Disc I includes only thin threads, and disc A includes both thick and thin. In the middle of disk A there is a bright stripe called the H-zone. It does not have thin threads. Disc I is separated by a thin stripe Z, which is a membrane containing structural elements that hold the ends of thin filaments together. The area between two Z-lines is called sarcomere .

Fig.4. Myofibril structure (cross section)

Fig.5. Structure of striated muscle (longitudinal section)

Each thick thread is surrounded by six thin ones, and each thin thread is surrounded by three thick ones. Thus, in a cross section, the muscle fiber has a regular hexagonal structure.

When a muscle contracts, the length of actin and myosin filaments does not change. There is only a displacement of them relative to each other: thin threads move into the space between the thick ones. In this case, the length of disk A remains unchanged, but disk I is shortened, and the H strip almost disappears. Such sliding is possible due to the existence of cross bridges (myosin heads) between thick and thin filaments. During contraction, the sarcomere length may change from approximately 2.5 to 1.7 μm.

The myosin filament has many heads with which it can bind to actin. The actin filament, in turn, has sections (active centers) to which myosin heads can attach. In a resting muscle cell, these binding centers are covered by tropomyosin molecules, which prevents the formation of bonds between thin and thick filaments.

In order for actin and myosin to interact, the presence of calcium ions is necessary. At rest they reside in the sarcoplasmic reticulum. This organelle is a membrane cavity containing a calcium pump, which, using the energy of ATP, transports calcium ions into the sarcoplasmic reticulum. Its inner surface contains proteins capable of binding Ca 2+. which somewhat reduces the difference in the concentrations of these ions between the cytoplasm and the reticulum cavity. Spreading across cell membrane The action potential activates the reticulum membrane located close to the cell surface and causes the release of Ca 2+ into the cytoplasm.

The troponin molecule has a high affinity for calcium. Under its influence, it changes the position of the tropomyosin filament on the actin filament in such a way that the active center, previously covered by tropomyosin, opens. A cross bridge is attached to the opened active center. This leads to the interaction of actin with myosin. After bond formation, the myosin head, previously located at right angles to the filaments, tilts and pulls the actin filament relative to the myosin filament by approximately 10 nm. The resulting atin-myosin complex prevents further sliding of the threads relative to each other, so its separation is necessary. This is only possible due to the energy of ATP. Myosin has ATPase activity, that is, it is capable of causing ATP hydrolysis. The energy released in this case breaks the bond between actin and myosin, and the myosin head is able to interact with a new part of the actin molecule. The work of the bridges is synchronized in such a way that the binding, tilting and breaking of all bridges of one thread occurs simultaneously. When the muscle relaxes, the calcium pump is activated, which reduces the concentration of Ca 2+ in the cytoplasm; consequently, connections between thin and thick threads can no longer be formed. Under these conditions, when the muscle is stretched, the threads slide smoothly relative to each other. However, such extensibility is only possible in the presence of ATP. If there is no ATP in the cell, then the actin-myosin complex cannot break. The threads remain rigidly linked to each other. This phenomenon is observed in rigor mortis.

Read also: Payments during maternity leave up to 3 years

Fig.6. Contraction of the sarcomere: 1 – myosin filament; 2 – active center; 3 – actin filament; 4 – myosin head; 5 - Z-line.

A) there is no interaction between thin and thick threads;

b) in the presence of Ca 2+ the myosin head binds to the active site on the actin filament;

V) the cross bridges bend and pull the thin thread relative to the thick one, as a result of which the length of the sarcomere decreases;

G) the bonds between the threads are broken due to the energy of ATP, the myosin heads are ready to interact with new active centers.

There are two modes of muscle contraction: isotonic(the length of the fiber changes, but the voltage remains unchanged) and isometric(the ends of the muscle are fixed, as a result of which it is not the length that changes, but the tension).

Power and speed of muscle contraction

Important characteristics of a muscle are the strength and speed of contraction. The equations expressing these characteristics were empirically obtained by A. Hill and subsequently confirmed by the kinetic theory of muscle contraction (Deshcherevsky model).

Hill's equation. connecting the strength and speed of muscle contraction, has the following form: (P+a)(v+b) = (P +a)b = a(v max +b). where v is the speed of muscle shortening; P – muscle force or load applied to it; v max — maximum speed of muscle shortening; P is the force developed by the muscle in the isometric contraction mode; a,b are constants. general power. developed by the muscle, is determined by the formula: N total = (P+a)v = b(P -P). Efficiency muscles maintains a constant value ( about 40%) in the range of force values ​​from 0.2 P to 0.8 P. During muscle contraction, a certain amount of heat is released. This quantity is called heat production. Heat production depends only on changes in muscle length and does not depend on load. Constants a And b have constant values ​​for a given muscle. Constant A has the dimension of force, and b– speed. Constant b depends largely on temperature. Constant A is in the range of values ​​from 0.25 P to 0.4 P. Based on these data, it is estimated maximum contraction speed for a given muscle: vmax = b(P/a) .

14. Fine structure of myofibrils. Proteins of thick and thin filaments - structure and functions + (muscle contraction and composition question 15)

The mechanism of muscle contractions. Functions and properties of skeletal muscles

Muscle contraction is a complex process consisting of a number of stages. The main components here are myosin, actin, troponin, tropomyosin and actomyosin, as well as calcium ions and compounds that provide muscles with energy. Let's consider the types and mechanisms of muscle contraction. Let's study what stages they consist of and what is necessary for a cyclical process.

Muscles are grouped into groups that have the same mechanism of muscle contraction. On the same basis, they are divided into 3 types:

• striated muscles of the body;
• striated muscles of the atria and cardiac ventricles;
• smooth muscles of organs, blood vessels and skin.

The striated muscles are part of the musculoskeletal system, being part of it, since in addition to them it also includes tendons, ligaments, and bones. When the mechanism of muscle contraction is implemented, the following tasks and functions are performed:

• the body moves;
• body parts move relative to each other;
• the body is supported in space;
• heat is generated;
• the cortex is activated by afferentation from receptive muscle fields.

Smooth muscle consists of:

• the motor apparatus of the internal organs, which includes the bronchial tree, lungs and digestive tube;
• lymphatic and circulatory systems;
• genitourinary system.

Physiological properties

Like all vertebrates, the human body has three most important properties of skeletal muscle fibers:

• contractility - contraction and change in tension during excitation;
• conductivity - movement of potential throughout the fiber;
• excitability is a response to a stimulus by changing the membrane potential and ionic permeability.

The muscles become excited and begin to contract from nerve impulses coming from the centers. But in artificial conditions, electrical stimulation is used. The muscle can then be stimulated directly (direct stimulation) or through the nerve innervating the muscle (indirect stimulation).

Types of abbreviations

The mechanism of muscle contraction involves the conversion of chemical energy into mechanical work. This process can be measured in an experiment with a frog: its calf muscle is loaded with a small weight and then stimulated with light electrical impulses. A contraction in which the muscle becomes shorter is called isotonic. With isometric contraction, no shortening occurs. Tendons do not allow the muscle to shorten as it develops strength. Another auxotonic mechanism of muscle contraction involves conditions of intense loads, when the muscle is shortened minimally and strength is developed to the maximum.

Structure and innervation of skeletal muscles

Striated skeletal muscles contain many fibers found in connective tissue and attached to tendons. In some muscles, the fibers are located parallel to the long axis, while in others they have an oblique appearance, attaching to the central tendon cord and to the pennate type.

The main feature of the fiber is the sarcoplasm, a mass of thin filaments - myofibrils. They include light and dark areas, alternating with each other, and the neighboring striated fibers are at the same level - at the cross section. This results in transverse striation throughout the entire muscle fiber.

The sarcomere is a complex of a dark and two light disks, and is delimited by Z-shaped lines. Sarcomeres are the contractile apparatus of muscles. It turns out that the contractile muscle fiber consists of:

• contractile apparatus (myofibril system);
• trophic apparatus with mitochondria, Golgi complex and weak endoplasmic reticulum;
• membrane apparatus;
• supporting apparatus;
• nervous apparatus.

Muscle fiber is divided into 5 parts with their own structures and functions and is an integral part of muscle tissue.

Innervation

This process in striated muscle fibers is realized through nerve fibers, namely the axons of motor neurons in the spinal cord and brain stem. One motor neuron innervates several muscle fibers. The complex with a motor neuron and innervated muscle fibers is called a neuromotor unit (NME), or motor unit (MU). The average number of fibers that one motor neuron innervates characterizes the size of the muscle MU, and the inverse value is called innervation density. The latter is large in those muscles where movements are small and “subtle” (eyes, fingers, tongue). On the contrary, its small value will be in muscles with “rough” movements (for example, the torso).

Innervation can be single or multiple. In the first case, it is realized by compact motor endings. This is usually characteristic of large motor neurons. Muscle fibers (called physical or fast muscle fibers in this case) generate action potentials (APs) that are propagated to them.

Multiple innervations occur, for example, in the external eye muscles. No action potential is generated here, since there are no electrically excitable sodium channels in the membrane. In them, depolarization spreads throughout the fiber from the synaptic endings. This is necessary in order to activate the mechanism of muscle contraction. The process here does not happen as quickly as in the first case. That's why it's called slow.

Myofibril structure

Studies of muscle fiber today are carried out on the basis of X-ray diffraction analysis, electron microscopy, and also histochemical methods.

It is calculated that each myofibril, whose diameter is 1 μm, contains approximately 2500 protofibrils, that is, elongated polymerized protein molecules (actin and myosin). Actin protofibrils are twice as thin as myosin protofibrils. At rest, these muscles are located in such a way that the actin filaments with their tips penetrate into the spaces between the myosin protofibrils.

The narrow light stripe in disk A is free of actin filaments. And the Z membrane holds them together.

Myosin filaments have transverse projections up to 20 nm long, the heads of which contain about 150 myosin molecules. They extend biopolarly, and each head connects a myosin filament to an actin filament. When there is a force on the actin centers on the myosin filaments, the actin filament moves closer to the center of the sarcomere. At the end, the myosin filaments reach the Z line. Then they occupy the entire sarcomere, and the actin filaments are located between them. In this case, the length of disk I is reduced, and at the end it disappears completely, at the same time the Z line becomes thicker.

Thus, according to the sliding filament theory, the reduction in muscle fiber length is explained. The theory, called the "gear wheel", was developed by Huxley and Hanson in the mid-twentieth century.

Mechanism of muscle fiber contraction

The main thing in the theory is that it is not the filaments (myosin and actin) that are shortened. Their length remains unchanged even when the muscles are stretched. But bundles of thin threads, slipping, come out between thick threads, the degree of their overlap decreases, and thus contraction occurs.

The molecular mechanism of muscle contraction through the sliding of actin filaments is as follows. Myosin heads connect the protofibril to the actin fibril. When they tilt, sliding occurs, moving the actin filament towards the center of the sarcomere. Due to the bipolar organization of myosin molecules on both sides of the filaments, conditions are created for actin filaments to slide in different directions.

When muscles relax, the myosin head moves away from the actin filaments. Thanks to easy gliding, relaxed muscles resist stretching much less. Therefore, they passively lengthen.

Stages of reduction

The mechanism of muscle contraction can be briefly divided into the following stages:

1. The muscle fiber is stimulated when an action potential is received from the motor neurons at the synapse.
2. An action potential is generated at the muscle fiber membrane and then propagates to the myofibrils.
3. Electromechanical coupling is performed, which is the transformation of electrical PD into mechanical sliding. Calcium ions are necessarily involved in this.

All muscles are divided into 2 types:

1. Smooth muscle, which is found in internal organs and the walls of blood vessels.
2. Striated – a) cardiac, b) skeletal

Skeletal (striated) muscles perform the following functions:

1. movement of a body in space
2. movement of body parts relative to each other
3. maintaining posture

The structural and functional unit of striated muscle is the neuromotor unit (NMU). It is represented by the axon of the motor neuron, its branches and the muscle fibers that are innervated by them.

Muscle fiber structure

Each muscle consists of muscle fibers arranged longitudinally, which are multinucleated cells. On the outside, they are covered with a basement membrane and plasmalemma, between which cambial cells (myosatellocytes) are located. On the plasma membrane in many places there are finger-shaped impressions - T-tubules. They connect the sarcolemma with the sarcoplasmic reticulum (SRR). Inside there is the usual set of organelles: numerous nuclei occupying a peripheral position, mitochondria, etc. SPR is a system of interconnected tubules with a high Ca+ content

The central part of the cytoplasm is occupied by specific organelles - myofibrils - contractile elements located longitudinally.

Fig. 10. Sarcomere structure

The structural unit of myofibrils is the sarcomere. It is a constantly repeating part of the myofibril, enclosed between two Z-membranes (telophragms). In the middle of the sarcomere there is a line M - mesophragm. Myosin filaments, a contractile protein, are attached to the mesophragm, and actin (also a contractile protein) is attached to the telophragm.

The alternation of these contractile proteins constitutes the transverse striation (Fig. 10). In the sarcomere, an anisotropic disk (A) is distinguished - a disk with birefringence (myosin + actin ends), an H-zone - only myosin filaments (part of disk A) and an I-disk - only actin filaments.

When the sarcomere contracts, disc I shortens and the light zone H decreases.

The contraction of the entire muscle is determined by the shortening of the sarcomere, and its length is reduced due to the formation of acto-myosin complexes.

Myosin is a thick protein molecule that is located in the center of the sarcomere and consists of two chains - light and heavy meromyosin. In cross section, myosin has the appearance of a daisy - the central part and hanging heads. The light meromyosin head has ATPase activity, which manifests itself only at the moment of contact with the active site of actin.

Actin is a globular protein consisting of two chains intertwined in the form of beads. Each globule has active sites that are covered by tropomyosin, and its position is regulated by troponin. In the resting state, active actin sites do not interact with the myosin head, since they are covered in the form of a lid by tropomyosin (Fig. 11).

The mechanism of muscle contraction.

When a motor neuron is excited, the impulses approach the myoneural plate (the place of contact between the axon and the plasmalemma). Acetylcholine (ACh) is released from the presynaptic membrane, which passes through the synaptic cleft and acts on the plasmalemma (at this point it can be called postsynaptic), finds receptors for ACh and interaction with them affects the permeability of the membrane to sodium ions. The permeability of the membrane to sodium increases, depolarization occurs, which leads to the occurrence of AP. It spreads along the membrane and is transmitted to T-tubules, which are closely associated with the SPR. PD in the area of ​​T-tubules causes an increase in the permeability of the SPR membrane for calcium, and it is released into the cytoplasm in quanta (portions) depending on the pulse frequency.

Calcium triggers the mechanism of sarcomere shortening. The concentration of calcium determines how much the sarcomere (and the muscle as a whole) contracts.

Calcium released into the cytoplasm finds the protein troponin, interacts with it and causes its conformational changes (that is, changes the spatial arrangement of the protein).

Conformational changes in troponin shift tropomyosin from its place, thereby opening the active (reactive) site of actin.

The myosin head is inserted into this open region. With this contact, enzymatic systems located in series are activated. And this gear-type contact between the two proteins mechanically moves the actin filament towards the center of the sarcomere. An actin step occurs.

The more actin steps occur, the more the sarcomere shortens.

At the moment of contact of the myosin head and the reactive region of actin, the head acquires ATPase activity.

What is ATP energy used for:

- comb-like movement and breaking of bonds between actin and myosin;

- for the operation of the calcium pump;

- for the operation of the sodium-potassium pump.

Thus, the more calcium is released, the more acto-myosin complexes are formed, the more strokes myosin makes, the more the sarcomere shortens.

As soon as the motor neuron stops sending impulses to the muscle fiber membrane, and the SPR stops receiving PD from T-tubules, the release of calcium from the SPR stops, and the work of the calcium pump increases, the acto-myosin bridges break, the Z-membrane returns to its place and the sarcomere relaxes. (and muscles in general).

Phases of muscle contraction.

Muscle contraction can be recorded on a kymograph. To do this, the muscle is attached to a tripod, and to the other end is a scribe, which records muscle contraction (Fig. 12).

The following phases are distinguished in muscle contraction:

- latent (0.01 sec) - from the onset of the stimulus to the visible response;

— contraction phase (0.04 sec);

— relaxation phase (0.05 sec).

Thus, a single muscle contraction takes 0.1 seconds. During the period of muscle contraction, the excitability of the tissue changes, that is, its ability to respond repeatedly when exposed to high-frequency stimuli.

At relatively low frequencies, the response will appear as a series of single muscle contractions (up to 10 impulses per second).

Tetanus. Optimum and pessimum frequencies.

If you increase the frequency of applied stimuli, you can select a frequency at which each subsequent stimulus will act during the relaxation phase. In this case, the muscle will contract from an incompletely relaxed state, and the response will be dentate tetanus. For calf muscle frogs, serrated tetanus occurs at a frequency of more than 10 but less than 20 impulses (each subsequent impulse arrives after 0.09 - 0.06 sec)

With a further increase in the frequency of more than 20 impulses per second (up to 50), smooth tetanus is recorded, since each impulse falls into the period of contraction, and the muscle contracts from the contracted state (each subsequent impulse arrives after 0.02 - 0.05 seconds).

The serrated tetanus is higher than a single muscle contraction, and the smooth tetanus is even higher. Tetanus is based on the summation (superposition) of contractions and a high concentration of calcium released from the SPR. As the frequency of the stimulus increases, the release of calcium from the SPR increases, which is released in quanta and does not have time to return back.

But not all high-frequency stimuli cause optimal contraction. Most often, smooth tetanus produces optimal contraction.

Frequency optimum is the maximum response to high-frequency stimuli.

Stimuli of very high frequency can reduce the response, and then a frequency pessimum occurs. At a frequency of 100 pulses per second, the stimulus hits the end of the latent phase (each subsequent pulse arrives after 0.01 sec), and a single muscle contraction occurs in response. At a frequency of 200 impulses/sec (each subsequent impulse arrives after 0.005 sec), either a single muscle contraction occurs or there is no reaction.

Reduced response during the period pessimum associated with the action of the stimulus during a period of either absolute or relative refractoriness. Absolute refractoriness takes 0.005 seconds. Then, during the period of relative refractoriness, excitability is below 100%. Excitability is restored after 0.01 seconds. (Fig. 13).

Fine muscle structure

The skeletal muscle of vertebrates consists of several thousand parallel muscle fibers with a diameter of 10-100 microns, enclosed in a common membrane. The ending of a nerve fiber is attached to each muscle fiber through the end plate. Muscle fiber is capable of contraction under the influence of a nerve impulse and represents a functional element of the muscular system. The length of the fiber can be equal to the length of the muscle itself or a significant part of it. The fibers at each end of the muscle pass into the tendon, which takes the tension during contraction.

The muscle fiber, in turn, contains 1000-2000 parallel muscle fibrils (myofibrils) with a diameter of about 1 micron. The entire bundle of myofiorilla is covered with a muscle fiber membrane - plasmalemma. The plasma membrane, like the membranes of all other cells, consists of three layers of proteins and lipids with a total thickness of about 10 nm and is electrically polarized. The membrane potential reaches 100 mV. The plasmalemma is covered on top with a thin layer of collagen filaments that have elastic properties.

The muscle fiber contains many nuclei located near the plasmalemma, and a large number of mitochondria located between the fibrils. Mitochondria are centers for the formation of high-energy compounds, primarily ATP. From here, high-energy compounds pass through the sarcoplasm to the fibrils.

Microscopic examination shows that dark and light stripes regularly alternate in skeletal muscle fibers, forming a characteristic transverse striation. The transverse striation of the fibers is caused by the transverse striation of myofibrils, located strictly next to each other.

Using the method of electron microscopy and the method of X-ray structural analysis, it was possible to find out that each myofibril consists of parallel thick and thin filaments - protofibrils, alternating in a strictly defined manner. Further studies revealed that thick filaments are formed by myosin protein molecules, and thin filaments by actin protein molecules. The length of myosin filaments is approximately 1.5 µm, and actin filaments 1 µm; thickness – 16 and 5-7 nm, respectively.

As a result of the alternation of thick and thin threads, transverse striations appear, visible under a microscope. The microscopic picture of striated muscle is characterized by an alternation of dense anisotropic stripes (called A-disks) and light isotropic stripes (I-discs). In A-disks, myosin filaments form a hexagonal (hexagonal) packing; They are what determine the high optical density of the disks. The active filaments are attached on each side to a narrow protein structure, the so-called Z-membrane, which crosses the I-band. The segment of myofibrils enclosed between two Z-membranes is called a sarcomere. In the muscle fiber, in the place where both types of protofibrils overlap each other, there are 2 times more thin protofibrils in the bundle than thick ones. Thin protofibrils end at the edge of the H-zone, an area of ​​lower optical density located in the middle of the A-band. In the center of the A-disc there is a narrow dark stripe known as the M line. This line is believed to correspond to a small thickening that is present in the center of each thick filament.

As Hanson and Levy showed, actin protofibrils have a double helix shape formed by globular actin molecules. The entire structure resembles two dense strings of beads twisted around one another, where the role of one bead is played by a globular actin molecule. Myosin protofibrils are also the result of aggregation of individual myosin molecules. To date, it has not been fully elucidated how the joining of myosin molecules in the protofibril occurs.

At a magnification of up to 600,000 times, micrographs of a longitudinal section of the muscle show that pairs of thick and thin protofibrils are connected by transverse bridges. These cross bridges are the only link between protofibrils and provide the structural integrity of the muscle. Subsequently, as a result of the application of X-ray structural analysis, it was shown that the bridges are formed by processes of myosin filaments located at intervals of 6-7 nm. The bridges connect the thick thread to each of the six thin threads, arranged in a spiral, the turns of which are repeated every 40 nm. There are no bridges in the central part of the myosin protofibrils, and in the electron micrograph these areas correspond to a “pseudo H-zone”, which has a lower optical density than the H-zone.

Enzymatic properties of actomyosin. Calcium pump

V.A. Engelhardt and M.N. Lyubimova (1939) made a very important discovery; they showed that, along with contractile properties, myosin has enzymatic properties, being the enzyme adenosine triphosphatase, which breaks down ATP. In myofibrils, through cross bridges, myosin forms a complex with actin. The energy released during ATP hydrolysis is directly used to contract the actomyosin complex. The enzymatic activity of actomyosin is approximately 10 times higher than the activity of myosin alone.

Enzymatic activity, and therefore the ability to contract the actomyosin complex, strongly depends on the presence of calcium ions in the medium. Many scientists believe that in the absence of calcium ions, actomyosin is not able to break down ATP and contract at all. When the calcium concentration increases to a certain limit, actomyosin activity increases and reaches its maximum value at a calcium concentration equal to the ATP concentration in the medium. It is assumed that calcium ions are part of the active centers of myosin, localized in the region of cross bridges, and only after this does myosin exhibit ATPase activity. The immediate cause of the breakdown of ATP and contraction of myofibrils is the appearance of free calcium ions in the sarcoplasm. Thus, injection of a solution containing calcium ions into the sarcoplasm leads to contraction of the muscle fiber in the absence of a nerve impulse and action potential of the muscle fiber. Finally, using special calcium indicators, it was shown that at the moment of fiber contraction there is an increase in the concentration of calcium ions in the sarcoplasm.

According to modern concepts, a special calcium pump functions in cells, the work of which causes contraction and relaxation of myofibrils. This pump, according to Bendoll, is localized in the membranes of the sarcoplasmic reticulum (endoplasmic reticulum) of the muscle fiber. The sarcoplasmic reticulum consists of tubes, cisterns, and vesicles located transversely and longitudinally in the sarcoplasm, the walls of which have a typical membrane structure. The transverse system of the sarcoplasmic reticulum is an invagination of the plasmalemma, going inward in the form of tubes and covering each fibril at the level of the junction of the A- and I-disks in the muscles of mammals and at the level of the Z-membranes in cold-blooded animals. Through the transverse tubules of the sarcoplasmic reticulum, excitation in the form of a depolarization wave is transmitted from the surface of the fiber excited by the nerve impulse to the myofibrils.

This is confirmed by Huxley's classic experiment with local irritation of frog muscle fibers. A microelectrode was used to apply a very weak subthreshold stimulation to various parts of the fiber. Local contraction of several myofibrils occurred only when stimulation was applied at the level of the Z-membranes, where the tubules of the transverse sarcoplasmic reticulum are localized. From the transverse reticulum, excitation is transmitted to the longitudinal reticulum located between the fibrils, where the calcium pump is localized. It is assumed that in the process of conducting excitation along the membranes of the reticulum, the main role is played not by sodium and potassium ions, but by calcium and magnesium ions.

Depolarization of the membranes of the tubules and vesicles of the sarcoplasmic reticulum leads to the release of calcium monomas contained in them. The mechanism for the release of calcium ions has not yet been established. This may be due to an increase in membrane permeability for calcium ions upon excitation and their subsequent diffusion along a concentration gradient into the sarcoplasm.

The appearance of free calcium ions in the sarcoplasm leads to the manifestation of ATPase activity of actomyosin and to the contraction of myofibrils. For myofibril contraction, the presence of magnesium ions is also necessary, the mechanism of action of which has not yet been established.

The process of relaxation of myofibrils is associated with the removal of calcium ions from the sarcoplasm, carried out by the sarcoplasmic reticulum. Reticulum elements have the ability to actively absorb calcium ions from the surrounding solution. Preparations of sarcoplasmic reticulum, isolated from muscles by differential centrifugation of their homogenates, have the ability to absorb calcium ions from solution. Moreover, in some cases, the concentration of calcium inside the vesicles and cisterns of the reticulum exceeded the concentration of calcium in the surrounding solution by 2000 times. The presence of active calcium transfer during relaxation of myofibrils is also confirmed by the fact that the calcium concentration in the sarcoplasm after microinjection begins to gradually decrease, which is accompanied by relaxation of myofibrils. It is possible, as Bendoll suggests, that reverse calcium transport is associated with the very movement of protofibrils during contraction, which eliminates the need for a special mechanism for active calcium transport.

The old idea that relaxation is caused by liberation specific factor relaxation - Marsh's factor - turned out to be wrong. This factor was isolated by extraction from muscle homogenates. It contained enzymes found in both sarcoplasm and fragments of the reticulum. One of these enzymes was taken as a relaxation factor, although in fact fragments of the reticulum had a relaxing effect.

It should be noted that relaxation of myofibrils when calcium ions are removed from the sarcoplasm occurs only if the sarcoplasm contains ATP. Removal of ATP from the sarcoplasm leads to the formation of strong electrostatic bonds between actin and myosin, which causes stiffness (contracture) of the muscle and loss of its ability to stretch.

Thus, contraction of myofibrils is caused by the breakdown of ATP in the presence of calcium ions, and relaxation is caused by the supply of new ATP molecules to protofibrils in the absence of calcium ions. The regulator of contraction and relaxation of myofibrils is the entry of calcium ions into the sarcoplasm and their removal into the sarcoplasmic reticulum.

The restoration of the original length of the muscle after contraction is probably due to the presence of elastic elements in the muscle fibers and the work of antagonist muscles. The elastic elements of the muscle fiber are the collagen membrane covering the plasma membrane and, possibly, the sarcoplasmic reticulum. If the sarcolemma is removed from the fiber and forced to contract, the fiber cannot relax spontaneously, although it is easily extended to its original length under the action of an external force.

Theories of the mechanism of muscle contraction

Before obtaining data on the fine structure of muscles, attempts were made to explain the processes of muscle contraction by the deformation of isolated molecular chains of proteins, that is, by the lengthening or shortening of individual protein molecules or aggregates of molecules. Often, data on the deformation of various polymers were transferred to muscle contraction, without taking into account the structure of muscle fibers.

There are many known polyelectrolyte polymer systems that have the ability to change length when the chemical composition of the surrounding solution changes. An example of such a system is an extended chain of polyacrylic acid. When the solution is acidified, such a chain shortens; in an alkaline environment, on the contrary, it stretches. If you hang a weight on it, you can get a machine that performs mechanical work when the pH of the solution changes. There are also redox models and ion models of muscles, in which the contraction factors are, respectively, changes in the redox potential and the concentration of free ions.

In all these models, the change in the length of polymers occurs mainly as a result of changes in the electrostatic interaction between polymer units or between turns of a helix and in the case of helical structures.

There are many hypotheses that attempt to explain muscle contraction based on the properties of individual molecular chains of contractile proteins. All these hypotheses are based on the idea that muscle contraction is based on processes of conformational changes in the structure of protein chains. Thus, back in 1929, Meyer put forward a hypothesis according to which muscle contraction is caused by deformation of peptide chains due to changes in the electrostatic interaction of ionogenic groups COOH and NH 2 with changes in pH.

It is currently believed that a change in pH during excitation of myofibrils is not enough to cause conformational transitions of proteins, but may be sufficient to release calcium ions, which can already cause deformation of the protein chain.

According to another idea, the act of contraction is a conformational transition of the protein structure from the α-configuration, when the threads are linearly elongated, to the β-configuration, when the threads are collected into a ball.

However, these hypotheses could not explain the real picture of the complex structure of muscle fiber at the molecular level, obtained recently. It is possible that during slow contraction of smooth muscles, actual deformation (active contraction of individual protofibrils) of protein chains occurs, as G.M. Frank believes, but for the contraction of skeletal muscles, ideas based on the hypothesis of thread sliding are much more justified.

G. Huxley and Hanson put forward the hypothesis of thread sliding. They noted that over a wide range of deformations, both during contraction and stretching of myofibrils, the width of the A-disk remains constant. On the contrary, when the sarcomere length changes, the width of the I-disc changes. The bright H-zone in the A-disk also changes, but it is remarkable that as long as it exists, the distance from the end of one H-zone through the Z-membrane to the beginning of the next H-zone (and this distance is equal to the length of the thin filaments in the myofibril ) also remains constant. If we remember that A-disks are formed by myosin filaments, and thin filaments are composed of actin, we can conclude that in a large area of ​​muscle deformation, the length of myosin and actin filaments remains constant. This can only be explained by the fact that when the muscle contracts, the threads simply slide relative to each other without changing their length.

When a muscle contracts strongly, a dense zone appears in the middle of the A-disc, and the width of this zone increases as the muscle contracts. This dense zone appears after the complete disappearance of the H-zone. The decrease in the H-zone during contraction is caused by the sliding of thin filaments towards each other towards the center of the A-disc. Having measured the distance from the Z-membrane to the opposite end of the new dense zone (contraction band), G. Huxley and Hchpsop found that it was equal to half the length of the thin protofibril. On this basis, they suggested that the new zone corresponds to the part of the sarcomere where the ends of the opposing thin filaments overlap each other. This assumption was confirmed by the fact that a micrograph of a cross section of the muscle in the area of ​​the new dense zone revealed 2 times more thin filaments than in the rest of the A-disc area. In addition, with strong muscle contraction, after the disappearance of the I-disc, dark stripes also appear in the area of ​​the Z-membranes. This is explained by the fact that myosin filaments reach the Z-membranes and after this they are deformed.

Subsequently, the electron microscopy data were confirmed by the results of X-ray diffraction analysis. The basic reflexes of the radiograph do not change with muscle contraction. This indicates that the length of the threads does not change during contraction. The data presented are very important, since, unlike electron microscopic studies carried out on fixed muscle preparations, radiographic studies were carried out both on living contracting muscles and on non-fixed muscle preparations.

The movement of thin filaments relative to thick ones occurs with the help of bridges connecting myosin filaments to actin filaments. Since there are no changes in the length of thick and thin filaments during contraction, it follows from the model of filament sliding that conformational changes that give rise to movement should occur in the indicated bridges connecting thick and thin filaments. The entire reduction process is cyclical. Myosin bridges are attached to the active sites of actin filaments and, under the influence of the energy of ATP hydrolysis, they shorten or change the angle of inclination to the myosin filaments, which leads to a certain movement of the filaments relative to each other. Then the bridges in these areas of actin filaments are detached and joined in new areas. This cyclic process is repeated many times, resulting in continuous movement of the threads relative to each other. X-ray studies confirmed the assumption of the movement of the bridges. According to G. Huxley, the splitting of one ATP molecule leads to one closing and opening of bridges and to the movement of threads to one elementary site.

The amount of tension developed by the muscle is determined by the number of closed (functioning) bridges. If a muscle overcomes an external force during contraction, then the number of bridges that are necessary to balance this force is closed. The maximum force developed by a muscle is determined by the number of bridges that can be closed under given conditions. Based on these ideas, it is not difficult to explain the inverse dependence of the tension developed by a muscle during contraction on the speed of contraction. It takes some time for the bridges to close. As the sliding speed of the threads increases, the number of closed bridges decreases, which causes a decrease in the tension developed by the muscle.

Depending on the length of the sarcomeres, the length of the areas in which the actin and myosin filaments overlap each other will be different and, therefore, the number of bridges involved in creating the tension developed by the muscle will be different. Given that the maximum force of a myofibril is determined by the number of functioning bridges, it should be expected that the maximum force of isometric contraction of a myofibril will vary with changes in sarcomere length. At a sarcomere length of 3.65 µm, the actin and myosin filaments no longer overlap each other and the fiber can be expected to be unable to develop force. The contraction force should be understood as the difference between the total force developed when the muscle is irritated and the elastic restoring force caused by the elastic elements of the muscle in the case of stretching beyond its normal length. As the Z-membranes come closer, the actin filaments penetrate deeper into the spaces between the myosin filaments and, finally, at a distance of 2.2 μm, all the bridges of the myosin filaments come into contact with the actin filament. If these bridges are responsible for the generation of the force, then we should expect that in the range from position I to position II the force will be proportional to the degree of overlap of the threads. With further shortening of the fiber, the number of bridges that can be closed does not change and the force must remain constant until the sarcomere length decreases to 2.05 μm. At this moment, the actin filaments converge at their ends and the force should decrease due to the fact that thin filaments that penetrated beyond the middle of the A-disc will be incorrectly oriented in relation to the myosin bridges. The force should gradually decrease until the distance reaches 1.65 µm, when the ends of the myosin filaments come into contact with the Z-membranes. With further contraction, the myosin filaments must become deformed; the force should decrease faster and completely disappear when the actin filaments reach the opposing Z-membranes.

All these assumptions were confirmed experimentally. Gordon, A. Huxley, Julian (1966) measured the tension developed by the muscle fiber during isometric contraction, and at the same time, the sarcomere length was recorded using phase-contrast microscopy.

However, despite great success In the study of the mechanism of muscle contraction, the mechanism of the work of bridges, as a result of which the energy of ATP hydrolysis is converted into mechanical work, has not yet been finally established.

Currently, there are a number of hypotheses trying to explain the specific mechanism of interaction between actin and myosin filaments.

The most deeply developed and substantiated is the Davis hypothesis. According to this hypothesis, the bridge between the myosin and actin filaments is formed by polypeptide chains at the end of the myosin molecule, twisted into a spiral. At rest, the bridge is extended; the spiral is in a stretched state. This is due to the electrostatic repulsion of two negative charges. One of them is in a fixed state at the base of the bridge, which has ATPase activity. Another negative charge is localized at the end of the bridge to which the ATP molecule is associated.

When the muscle is excited, the sarcoplasmic reticulum releases calcium ions. They form a bond between the ATP molecule located at the end of the bridge and the ADP molecule located on the actin filament, which causes the neutralization of negative charges. Electrostatic repulsion disappears and the stretched chain - the bridge - twists into an α-helix due to the formation of hydrogen bonds. This process represents the release of potential energy stored by an elongated polypeptide chain during the initial repulsion of charges. Shortening the polypeptide chain to form an α-helix leads to two effects. Firstly, the actin filament moves relative to the myosin filament by one step; secondly, the attached ATP molecule moves to the region of the hypothetical ATPase center. Due to the appropriate location of this center and the inclination of the bridges relative to the thick filament, the actin filaments move towards the M lines. ATP is then broken down into ADP and the mineral phosphate, which leads to the breaking of the bonds between actin and myosin. In place of the ADP molecule in the myosin bridge, a new ATP molecule arrives from the sarcoplasm, which is repelled by the negative fixed charge of myosin. As a result, the α-helix stretches and the bridge lengthens. If there are free calcium ions in the sarcoplasm at this time, then the whole cycle repeats from the beginning.

In this case, the next section of the active thread participates in the interaction. If calcium ions have been removed from the sarcoplasm by this time, the fiber relaxes.

Davis' model received a number of additions and underwent modifications. Bendoll (1970) suggests that the addition of calcium ions in the bridge region leads to a change in the electrical interaction. Neutralization of negative charges and the attachment of actin to myosin determine the transformation of the helix of the polypeptide chain (bridge) of the myosin molecule into a more disordered, highly folded conformation using the “helix-coil” transition type.

Such a transition is accompanied by the release of potential (free) energy stored in a more ordered structure - a spiral.

This energy is partially spent on pulling force - moving the actin filament one step, and partially degraded into heat. The change in the conformation of the bridge simultaneously causes ATP to approach the ATPase site of myosin, which causes ATP hydrolysis.

Part of the released energy is dissipated in the form of heat, and part of it goes to restore the helical configuration of the bridge, which straightens as ATP is resynthesized or new ATP molecules arrive from the outside. The actomyosin complex disintegrates and the cycle can repeat if calcium ions are present in the system.

In the absence of ATP molecules in the system, it will be in a state of rigor - actin molecules will remain attached to the myosin binding centers.

With very strong muscle contractions, not only the advancement of actin filaments is noted, but also the shortening of sarcomeres as a whole.

Muscle contraction is a vital function of the body associated with defensive, respiratory, nutritional, sexual, excretory and other physiological processes. All types of voluntary movements - walking, facial expressions, movements of the eyeballs, swallowing, breathing, etc. are carried out by skeletal muscles. Involuntary movements (except for heart contraction) - peristalsis of the stomach and intestines, changes in the tone of blood vessels, maintenance of bladder tone - are caused by contraction of smooth muscles. The work of the heart is ensured by the contraction of the cardiac muscles.

Structural organization of skeletal muscle

Muscle fiber and myofibril (Fig. 1). Skeletal muscle consists of many muscle fibers that have points of attachment to bones and are located parallel to each other. Each muscle fiber (myocyte) includes many subunits - myofibrils, which are built from blocks (sarcomeres) repeating in the longitudinal direction. The sarcomere is the functional unit of the contractile apparatus of skeletal muscle. The myofibrils in the muscle fiber lie in such a way that the location of the sarcomeres in them coincides. This creates a pattern of cross striations.

Sarcomere and filaments. Sarcomeres in the myofibril are separated from each other by Z-plates, which contain the protein beta-actinin. In both directions, thin actin filaments. In the spaces between them there are thicker myosin filaments.

Actin filament externally resembles two strings of beads twisted into a double helix, where each bead is a protein molecule actin. Protein molecules lie in the recesses of actin helices at equal distances from each other. troponin, connected to thread-like protein molecules tropomyosin.

Myosin filaments are formed by repeating protein molecules myosin. Each myosin molecule has a head and tail. The myosin head can bind to an actin molecule, forming a so-called cross bridge.

The cell membrane of the muscle fiber forms invaginations ( transverse tubules), which perform the function of conducting excitation to the membrane of the sarcoplasmic reticulum. Sarcoplasmic reticulum (longitudinal tubules) It is an intracellular network of closed tubes and performs the function of depositing Ca++ ions.

Motor unit. The functional unit of skeletal muscle is motor unit (MU). MU is a set of muscle fibers that are innervated by the processes of one motor neuron. Excitation and contraction of the fibers that make up one motor unit occur simultaneously (when the corresponding motor neuron is excited). Individual motor units can be excited and contracted independently of each other.

Molecular mechanisms of skeletal muscle contraction

According to thread sliding theory, muscle contraction occurs due to the sliding movement of actin and myosin filaments relative to each other. The thread sliding mechanism involves several sequential events.

Myosin heads attach to actin filament binding centers (Fig. 2 A).

The interaction of myosin with actin leads to conformational rearrangements of the myosin molecule. The heads acquire ATPase activity and rotate 120°. Due to the rotation of the heads, the actin and myosin filaments move “one step” relative to each other (Fig. 2, B).

The uncoupling of actin and myosin and restoration of the head conformation occurs as a result of the attachment of an ATP molecule to the myosin head and its hydrolysis in the presence of Ca++ (Fig. 2, B).

The cycle “binding – change in conformation – uncoupling – restoration of conformation” occurs many times, as a result of which actin and myosin filaments move relative to each other, the Z-disks of sarcomeres come closer and the myofibril shortens (Fig. 2, D).

Coupling of excitation and contraction in skeletal muscle

In the resting state, thread sliding in the myofibril does not occur, since the binding centers on the actin surface are closed by tropomyosin protein molecules (Fig. 3, A, B). Excitation (depolarization) of the myofibril and muscle contraction itself are associated with the process of electromechanical coupling, which includes a series of sequential events.

As a result of the firing of a neuromuscular synapse on the postsynaptic membrane, an EPSP arises, which generates the development of an action potential in the area surrounding the postsynaptic membrane.

Excitation (action potential) spreads along the myofibril membrane and, through a system of transverse tubules, reaches the sarcoplasmic reticulum. Depolarization of the sarcoplasmic reticulum membrane leads to the opening of Ca++ channels in it, through which Ca++ ions enter the sarcoplasm (Fig. 3, B).

Ca++ ions bind to the protein troponin. Troponin changes its conformation and displaces the tropomyosin protein molecules that covered the actin binding centers (Fig. 3, D).

Myosin heads attach to the opened binding centers, and the contraction process begins (Fig. 3, E).

The development of these processes requires a certain period of time (10–20 ms). The time from the moment of excitation of a muscle fiber (muscle) to the beginning of its contraction is called latent period of contraction.

Skeletal muscle relaxation

Muscle relaxation is caused by the reverse transfer of Ca++ ions through the calcium pump into the channels of the sarcoplasmic reticulum. As Ca++ is removed from the cytoplasm open centers binding becomes less and less and eventually the actin and myosin filaments are completely disconnected; muscle relaxation occurs.

Contracture called a persistent, long-term contraction of a muscle that persists after the cessation of the stimulus. Short-term contracture can develop after tetanic contraction as a result of the accumulation of large amounts of Ca++ in the sarcoplasm; long-term (sometimes irreversible) contracture can occur as a result of poisoning and metabolic disorders.

Phases and modes of skeletal muscle contraction

Phases of muscle contraction

When skeletal muscle is irritated by a single pulse of electric current of suprathreshold strength, a single muscle contraction occurs, in which 3 phases are distinguished (Fig. 4, A):

Latent (hidden) period of contraction (about 10 ms), during which the action potential develops and electromechanical coupling processes occur; muscle excitability during a single contraction changes in accordance with the phases of the action potential;

Shortening phase (about 50 ms);

Relaxation phase (about 50 ms).

Modes of muscle contraction

Under natural conditions, a single muscle contraction is not observed in the body, since a series of action potentials occur along the motor nerves innervating the muscle. Depending on the frequency of nerve impulses coming to the muscle, the muscle can contract in one of three modes (Fig. 4, B).

Single muscle contractions occur at low frequency electrical impulses. If the next impulse enters the muscle after the completion of the relaxation phase, a series of successive single contractions occurs.

At a higher pulse frequency, the next pulse may coincide with the relaxation phase of the previous contraction cycle. The amplitude of contractions will be summed up, and there will be serrated tetanus- prolonged contraction, interrupted by periods of incomplete muscle relaxation.

With a further increase in the pulse frequency, each subsequent pulse will act on the muscle during the shortening phase, resulting in smooth tetanus- prolonged contraction, not interrupted by periods of relaxation.

Optimum and pessimum frequency

The amplitude of tetanic contraction depends on the frequency of impulses irritating the muscle. Optimum frequency they call the frequency of irritating impulses at which each subsequent impulse coincides with the phase of increased excitability (Fig. 4, A) and, accordingly, causes tetanus of the greatest amplitude. Pessimum frequency called a higher frequency of stimulation, at which each subsequent current pulse falls into the refractory phase (Fig. 4, A), as a result of which the amplitude of the tetanus decreases significantly.

Skeletal muscle work

The strength of skeletal muscle contraction is determined by 2 factors:

The number of units involved in the reduction;

Frequency of contraction of muscle fibers.

The work of skeletal muscle is accomplished through a coordinated change in tone (tension) and length of the muscle during contraction.

Types of skeletal muscle work:

dynamic overcoming work occurs when a muscle, contracting, moves the body or its parts in space;

static (holding) work performed if, due to muscle contraction, parts of the body are maintained in a certain position;

dynamic yielding operation occurs when a muscle functions but is stretched because the force it makes is not enough to move or hold parts of the body.

During work, the muscle can contract:

isotonic– the muscle shortens under constant tension (external load); isotonic contraction is reproduced only in experiment;

isometrics– muscle tension increases, but its length does not change; the muscle contracts isometrically when performing static work;

auxotonic– muscle tension changes as it shortens; auxotonic contraction is performed during dynamic overcoming work.

Rule of average loads– the muscle can perform maximum work under moderate loads.

Fatigue– a physiological state of a muscle that develops after prolonged work and is manifested by a decrease in the amplitude of contractions, an extension of the latent period of contraction and the relaxation phase. The causes of fatigue are: depletion of ATP reserves, accumulation of metabolic products in the muscle. Muscle fatigue during rhythmic work is less than synapse fatigue. Therefore, when the body performs muscular work, fatigue initially develops at the level of the synapses of the central nervous system and neuromuscular synapses.

Structural organization and contraction of smooth muscle

Structural organization. Smooth muscle consists of single spindle-shaped cells ( myocytes), which are located in the muscle more or less chaotically. Contractile filaments are arranged irregularly, as a result of which there is no transverse striation of the muscle.

The mechanism of contraction is similar to that of skeletal muscle, but the rate of filament sliding and the rate of ATP hydrolysis are 100–1000 times lower than in skeletal muscle.

The mechanism of coupling of excitation and contraction. When the cell is excited, Ca++ enters the cytoplasm of the myocyte not only from the sarcoplasmic reticulum, but also from the intercellular space. Ca++ ions, with the participation of the calmodulin protein, activate the enzyme (myosin kinase), which transfers the phosphate group from ATP to myosin. Phosphorylated myosin heads acquire the ability to attach to actin filaments.

Contraction and relaxation of smooth muscles. The rate of removal of Ca++ ions from the sarcoplasm is much less than in skeletal muscle, as a result of which relaxation occurs very slowly. Smooth muscles perform long tonic contractions and slow rhythmic movements. Due to the low intensity of ATP hydrolysis, smooth muscles are optimally adapted for long-term contraction, which does not lead to fatigue and high energy consumption.

Physiological properties of muscles

The general physiological properties of skeletal and smooth muscles are excitability And contractility. Comparative characteristics of skeletal and smooth muscles are given in table. 6.1. The physiological properties and characteristics of the cardiac muscle are discussed in the section “Physiological mechanisms of homeostasis.”

Table 7.1.Comparative characteristics of skeletal and smooth muscles

Plastic smooth muscles is manifested in the fact that they can maintain constant tone both in a shortened and in an extended state.

Conductivity smooth muscle tissue is manifested in the fact that excitation spreads from one myocyte to another through specialized electrically conductive contacts (nexuses).

Property automation smooth muscle is manifested in the fact that it can contract without the participation of the nervous system, due to the fact that some myocytes are able to spontaneously generate rhythmically repeating action potentials.