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Pathway Description
Striated Muscle Contraction
Homo sapiens
Physiological Pathway
Tubular striated muscle cells (i.e. skeletal and cardiac myocytes) are composed of bundles of rod-like myofibrils. Each individual myofibril consists of many repeating units called sarcomeres. These functional units, in turn, are composed of many alternating actin and mysoin protein filaments that produce muscle contraction. The muscle contraction process is initiated when the muscle cell is depolarized enough for an action potential to occur. When acetylcholine is released from the motor neuron axon terminals that are adjacent to the muscle cells, it binds to receptors on the sarcolemma (muscle cell membrane), causing nicotinic acetylcholine receptors to be activated and the sodium/potassium channels to be opened. The fast influx of sodium and slow efflux of potassium through the channel causes depolarization. The resulting action potential that is generated travels along the sarcolemma and down the T-tubule, activating the L-type voltage-dependent calcium channels on the sarcolemma and ryanodine receptors on the sarcoplasmic reticulum. When these are activated, it triggers the release of calcium ions from the sarcoplasmic reticulum into the cytosol. From there, the calcium ions bind to the protein troponin which displaces the tropomysoin filaments from the binding sites on the actin filaments. This allows for myosin filaments to be able to bind to the actin. According to the Sliding Filament Theory, the myosin heads that have an ADP and phosphate attached binds to the actin, forming a cross-bridge. Once attached, the myosin performs a powerstroke which slides the actin filaments together. The ATP and phosphate are dislodged during this process. However, ATP now binds to the myosin head, which causes the myosin to detach from the actin. The cycle repeats once the attached ATP dissociates into ADP and phosphate, and the myosin performs another powerstroke, bringing the actin filaments even closer together. Numerous actin filaments being pulled together simultaneously across many muscles cells triggers muscle contraction.
References
Striated Muscle Contraction References
Cooke R: The sliding filament model: 1972-2004. J Gen Physiol. 2004 Jun;123(6):643-56. doi: 10.1085/jgp.200409089.
Pubmed: 15173218
Szent-Gyorgyi A: The mechanism of muscle contraction. Proc Natl Acad Sci U S A. 1974 Sep;71(9):3343-4.
Pubmed: 4610574
Kuo IY, Ehrlich BE: Signaling in muscle contraction. Cold Spring Harb Perspect Biol. 2015 Feb 2;7(2):a006023. doi: 10.1101/cshperspect.a006023.
Pubmed: 25646377
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