Mechanism of Muscle Contraction
Introduction :
Mechanism of Muscle Contraction – Activation of tension-generating sites within muscle fibers activates the contractile forces in a muscle leading to muscular contraction. The muscle tension can be produced without any change in muscle length. The muscle fibers returns back to their low tension generating state with termination of muscle contraction and occurrence of relaxation.
The individual cells that comprise muscles are called muscle fibers. Myofibrils, which are composed of repeating units called sarcomeres, are found inside every muscle fiber. The sarcomere is the basic contractile unit of the muscle and consists of two key protein filaments:
1. The thin filament actin
2. Thick filament myosin
Myofibrils :
The alternating light and dark shades (transverse stripes) and thick longitudinal stripes that are characteristic of skeletal muscle can be examined with a light microscope.
1. Electron microscopy reveals that the longitudinal stripes are due to the presence of myofibrils of different thicknesses, and the transverse stripes are due to the presence of alternating light and dark segments of longitudinally arranged elements.
2. In cross section, the myofibrils appear as minute dots that are either uniformly distributed or present in groups of polygonal areas. They are separated from adjacent bundles by transparent sarcoplasm.
3. The dark bands are doubly refractive (anisotropic) when examined under polarized light and are therefore called A bands.
4. The light bands are singly refractive (isotropic) under a polarized light microscope, hence the name I band.
5. This I band is divided in part in the middle by the Z line, with a thin, black line.
6. The membranes that make up the Z lines run the whole length of the myofibril. These Z lines correspond to the myofibril coils. The term “sarcomere” refers to the portion of a myofibril that is bounded by two neighboring Z lines and is referred to as the contractile unit. It has a length of 2-3 μm.
7. In certain exceptional specimens, the central part of the A band becomes lighter in color and is called the H band (Hensen’s line).
8. In the middle of the H band, i.e. H Also in the A band, there is a thin dark line, the M line or M band, where the myosin filaments have thickened.
9. The myosin and actin filaments overlap in a dark region around the A band, called the O band.
10. In the center of the I band, on either side of the Z line, there are relatively dark regions.
thin horizontal lines, i.e. N lines.
Electron microscopy has shown that thin, thread-like protein filaments come together to form myofilaments, with the thicker sections being myosin filaments (100 Å in diameter) and the thinner sections being actin filaments (50 Å in diameter).
1. The thin filament actin
Actin filaments extend from each Z line in the sarcomere towards the H band and are connected to
other actin filaments by 5 filaments in the H band. They stretch 1 micrometer on both sides of the Z line.
Characteristics:
1. According to Knappeis and Carlsen, actin filaments are approximately 1 μm long.
2. Under very high magnification, F-actin – Filamentous actin appears as beads and consists of globular subunits (55A)-G-actin. They form two chains that intertwine to form a helix. These chains are thus polymers of G-actin. They contain 13 G-actins. in every turn of the helix.
3. Low-angle x-ray and chemical studies suggest that tropomyosin and the newly discovered troponin line the grooves of the actin helices.
4. As the actin filaments approach the Z line, they appear continuous with four thin branching filaments (Z filaments). These Z filaments are thought to contain the muscle protein tropomyosin.
5. The arrangement of myosin filaments forms a triangle across the actin filament, however when examined in cross section, the actin filament arrangement seems hexagonal around the myosin.
6. The thin actin filaments are connected to each other longitudinally by even thinner S filaments.
2. Thick filament myosin
Myosin filaments are parallel strands that make up each segment of the A band.
Characteristics :-
1. Myosin filaments are about 1.5 μm (15,000 Å) long, thickening slightly at the midline.
2. When these filaments dissociate further, the myosin molecule (1500 Å long) appears rod-like with a spherical projection at one end.
3.The beaded structure around the myosin filament is due to the presence of a globular head of the myosin molecule. The rod-shaped part is called light (L) meromyosin and the head is called meromyosin (H). The globular part is called heavy (H) meromyosin.
4.Heavy meromyosin consists of two components. High meromyosin subfragment I refers to the head, and high meromyosin subfragment II refers to the neck. Heavy meromyosin subfragment I has all the enzymatic and actin-binding properties of the parent molecule (myosin).
5. Each 400 A segment of a myosin filament has six heavy meromyosin heads (cross-bridges). These heavy meromyosin heads are helically arranged in a 60 degree radial pattern, with each set of six bridges completing one revolution around the myosin filament.
6. Each head of heavy meromyosin is directed toward a separate actin filament, so that actin cross-bridges occur at intervals of about 400 Å along the myosin filament.
7. Heavy meromyosin is also responsible for the ability to form actin cross-bridges and the ATPase activity that is essential for muscle contraction. This heavy meromyosin is sometimes called the active site of the myosin molecule.
8. In the M-band region (middle of myosin filament) where tail to tail binding of myosin molecules occurs, myosin filament appears thicker in this region suggesting the possible presence of proteins of unknown nature (these proteins) which may help in strengthening the tail to tail binding of myosin molecules.
Mechanism of Contraction :
The myofilament (contractile protein) folding theory states that certain muscle proteins are shortened or folded by forming actin-myosin complexes during muscle contraction. However, morphological studies have not shown evidence that myosin filaments are shortened during muscle contraction. Even if actin filaments were to shorten or fold, this would not be possible in normal life.
• Interdigitation or Sliding of Myofilaments: The filament sliding hypothesis states that the relative positions of myofilaments change during muscle contraction, but neither actin nor myosin filaments themselves are shortened. Cross-bridge interactions between actin and myosin cause muscle contraction through a filament sliding mechanism.
• During contraction, actin filaments slide past myosin filaments, which causes them to extend further into the A-band, shortening the length of the H-zone and narrowing the sarcomere.
• During this process, the myosin filaments gradually approach the Z-line and the actin filaments approach the M-line, shifting the attachment position of the crossbridges at a single point in the front like moving gears.
• At certain stages of contraction, the ends of two adjacent actin filaments may come into contact and the length of the I-band is at a minimum.
There are two theories regarding the position of two opposing actin filaments from the same sarcomere during maximal contraction.
• At their free ends, filaments made of actin in the M-band glide past one another.
• The zigzag lines straighten out, increasing the distance between adjacent actin filaments.
The sarcomere shortens as a result of the actin filaments becoming longer in the direction of the Z lines. Contraction is therefore achieved by the thin filaments from opposite sides of each sarcomere sliding closer together between the thick filaments. The myosin ATPase enzyme found on the local bulky meromyosin molecules breaks down ATP to supply the energy needed for this sliding motion.
Molecular Mechanism for Muscle Contraction :-
The following activity steps are involved in the contraction of skeletal muscle:
1. An action potential reaching the axon of a motor neuron activates voltage-gated calcium ion channels on the axon, allowing calcium to enter.
2. The axon’s cholinergic vesicles fuse with the membrane in response to calcium, spilling acetylcholine into the space between the axon and the muscle fiber’s motor endplate.
3. Acetylcholine then diffuses through the gap and binds to nicotinic receptors at the motor endplate of the membrane, allowing sodium to enter and potassium to fly out. However, sodium is more permeable, so the sarcolemma becomes more positively charged, triggering an action potential.
4. As already mentioned, the function of the T system is to transmit impulses from the sarcolemma to the myofilaments within a short period of time. After stimulation, an impulse is transmitted from the T system to the myofibril, where depolarization releases calcium from the sarcoplasmic reticulum and activates myosin ATPase. This activated ATPase splits ATP into ADP and ADP into AMP, releasing a certain amount of energy required for the contraction process.
5. Troponin, which is found on the fine filaments of the myofibrils, binds to the released calcium. Troponin then allosterically regulates tropomyosin. In the resting state, tropomyosin physically blocks the binding sites of the cross-bridges. Then, when calcium binds to troponin, troponin forces tropomyosin to move, freeing the binding sites.
6. The myosin head forms a cross-bridge with the actin-binding site.
7. ATP binds to the myosin head and breaks the cross-bridge.
8. Hydrolysis of ATP causes the myosin head to change shape and rotate to move to the next actin-binding site.
9. The actin filaments glide over the myosin filaments as a result of the myosin head’s movement, shortening the sarcomere’s length and triggering repeated ATP hydrolysis in the skeletal muscle to contract.
Molecular Mechanism for Muscle Relaxation :-
Relaxant factors have been isolated from muscle homogenates. Electron microscopy studies of muscle homogenates show the presence of membrane-bounded vesicles resulting from fragmentation of the sarcoplasmic reticulum. These vesicles can bind Ca++ in the presence of ATP. Calcium ATPase pumps calcium out of the sarcoplasmic reticulum and into the sarcoplasmic reticulum. Calcium ATPase activity decreases because action potentials no longer reach the neuromuscular junction. The connection among the head regions of myosin and the active sites of the actin filaments stops because there are not enough calcium ions that interact with troponin, causing the muscle to relax.
The relationship between muscle contraction and ATP breakdown :-
The mechanism of muscle contraction begins with the breakdown of ATP. Contraction occurs through the release of phosphate bond energy from ATP. When a muscle is stimulated, an impulse traveling along the fiber increases the sodium and calcium permeability of the membrane. As a result, the influx of sodium ions into the interior of the muscle fiber is accompanied by a small influx of calcium ions at the same time. The calcium ions then stimulate adenosine triphosphatase (ATPase), which aids in the release of energy from the ATP surrounding the myofilament. This energy creates a temporary electrostatic charge between the actin and myosin filaments, pulling the actin filaments into the spaces between the myosin filaments. ATPase remains active as long as calcium ions are present inside the muscle fiber. Surrounding the filaments and sarcoplasmic reticulum are other substances known as relaxants, which bind with the calcium ions within seconds of penetrating the fiber, converting calcium to its non-ionized form. As a result of the inactivation of calcium ions in the muscle fiber, adenosine triphosphate no longer releases energy. The static charge between the actin and myosin filaments disappears, and the muscle relaxes. Phosphate bonds come in two varieties: low-energy bonds and high-energy bonds, which are represented by the symbol -.
1. Breaking a high-energy bond releases about 10,000-12,000 cal/g/mol, whereas a low-energy bond releases only 2,000 cal/g/mol.
2. While phosphagens have one high-energy phosphate bond (Cr-P), ATP has two high-energy bonds of phosphate and one low-energy phosphate link (ATP = A-P-P-P). It is believed that the energy released from high-energy bonds is used for work and other cellular processes rather than being wasted as heat.
Conclusion :-
In summary, the mechanism of muscle contraction is a highly coordinated process involving the interplay of electrical, chemical, and mechanical events. It is regulated by precise control of calcium ions and a continuous supply of ATP. The sliding filament model provides a fundamental framework for understanding how muscles generate force and movement. Research advances have improved our understanding of this process, enabling the development of therapies for treating muscle-related diseases and improving muscle function. Understanding muscle contraction not only reveals important aspects of human physiology, but also highlights the complexity of cellular function and the body’s ability to adapt to different physical demands.