Each muscle fiber is multinucleate and behaves as a single unit. It contains bundles of myofibrils, surrounded by sarcoplasmic reticulum (SR) and invaginated by transverse tubules (T tubules). Each myofibril contains interdigitating thick and thin filaments arranged longitudinally in sarcomeres. Repeating units of sarcomeres account for the unique banding pattern in striated muscle. Sarcomere runs from Z line to Z line.
Thick Filaments are present in the A band in the center of the sarcomere. It contain myosin. Myosin has 6 polypeptide chains, including the one pair of heavy chains and two pairs of light chains. Each myosin molecule has two “heads” attached to a single “tail.” The myosin heads bind ATP and actin, and are involved in cross-bridge formation.
Thin Filaments are anchored at the Z line. They are present in the I band. They interdigitate with the thick filaments in a portion of the A band. It contain actin, tropomyosin, and troponin. Troponin is the regulatory protein that permits cross-bridge formation when it binds calcium. It has 3 globular proteins: Troponin T, I, C. Troponin T (tropomyosin) attaches the troponin complex to tropomyosin. Troponin I (inhibition) inhibits the interaction of actin and myosin. Troponin C (calcium) is the calcium-binding protein that, when bound to calcium, permits the interaction of actin and myosin.
T tubules are an extensive tubular network, open to the extracellular space that carry the depolarization from the sarcolemmal membrane to the cell interior. They are located at the junctions of A band and I band. It contains voltage-sensitive protein called dihydropyridine receptor; depolarization causes conformational change in the dihydropyridine receptor.
Sarcoplasmic Reticulum is the internal tubular structure that is the site of calcium storage and release for excitation-contraction coupling. It has terminal cisternae that make intimate contact with the T tubules in a triad arrangement. Its membrane contains Ca++ ATPase (Ca++ pump), which transports Ca++ from intracellular fluid into the SR interior, keeping intracellular calcium low. It contains calcium bound loosely to calsequestrin. It contains a calcium release channel called ryanodine receptor.
Steps in excitation-contraction coupling in skeletal muscle
1. Action potential in the muscle cell membrane initiate depolarization of the T tubules.
2. Depolarization of the T tubules causes a conformational change in its dihydropyridine receptor, which opens Calcium release channels (ryanodine receptor) in the nearby SR, causing release of calcium from the SR into the intracellular fluid.
3. Intracellular calcium increases.
4. Calcium binds to troponin C on the thin filaments, causing a conformational change in troponin that moves tropomyosin out of the way. The cross-bridge cycle begins.
(2) ATP then binds to myosin, producing a conformational change in myosin that causes myosin to be released from actin.
(3) Myosin is displaced toward the plus end of actin. There is hydrolysis of ATP to ADP and inorganinc phosphate. ADP remains attached to myosin.
(4) Myosin attached to a new site on actin, which constitutes the power stroke (force-generating). ADP is then released, returning myosin to its rigor state.
(5) The cycle repeats as long as calcium is bound to troponin C. Each cross-bridge cycle “walks” myosin further along the actin filament.
5. Relaxation occurs when calcium is reaccumulated by the SR Ca++ ATPase (SERCA). Intracellular calcium concentration decreases, calcium is released from troponin C, and tropomyosin again blocks the myosin-binding site on actin. As long as intracellular calcium concentration is low, cross-bridge cycling cannot occur.
6. Mechanism of tetanus. A single unit action potential causes the release of a standard amount of calcium from SR and produces a single twitch. However, if the muscle is stimulated repeatedly, more calcium is released from the SR and there is a cumulative increase in intracellular, extending the time for cross-bridging.
Length-tension and force-velocity relationships in muscle
Isometric contractions are measured when length is held constant. Muscle length (preload) is fixed, the muscle is stimulated to contract, and the developed tension is measured. There is no shortening.
Isotonic contractions are measured load is held constant. The load against which the muscle contracts (afterload) is fixed, the muscle is stimulated to contract, and shortening is measured.
Length-tension relationship measures tension developed during isometric contractions when the muscle is set to fixed lengths (preload)
- Passive Tension is the tension developed by stretching the muscle to different lengths.
- Total Tension is the tension developed when the muscle is stimulated to contract at different lengths.
- Active Tension is the difference between total tension and passive tension. It represents the active force developed from contractions of the muscle. It is proportional to the number of cross-bridges formed. Tension will be maximum when there is maximum overlap of thick and thin filaments. When the muscle is stretched to greater lengths, the number of cross-bridges is reduced because there is less overlap. Then muscle length is decreased, the thin filaments collide and tension is reduced.
Force-velocity relationship measures the velocity of shortening of isotonic contractions when the muscle is challenged with different afterloads (the load against which the muscle must contract). The velocity of shortening decreases as the afterload increases.
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