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Skeletal Muscle Contraction Dr. Wasif Haq Introduction • Muscles make 50% of total body mass. • 40% by skeletal muscles & 10% combination of smooth & cardiac muscles. • Sarcolemma: Cell membrane of muscle fiber. Ends fuse with tendons’ fiber to form muscle tendons inserting in bone. • Sarcoplasm: Intracellular matrix of muscle fiber having suspended myofibrils. Abundant ATP & K+,P+,Mg++. • Sarcoplasmic reticulum: Endoplasmic reticulum of muscles, store Ca++ needed for contraction. • Sarcomere: Myofibrils comprise of smaller contractile units, smallest contractile unit of muscle fiber. Structure of Myofibril. • Sarcomeres comprise of series of alternating dark and light bands causing striated appearance. • Dark band=A band. (Anisotropic) comprise of Myosin & ends of Actin. • Lighter appearance in midsection called H-zone which is bisected by dark M line. • Light band=I band (Isotropic) comprise of Actin only. • Light band have middle Z line. Structure of Myofilaments • Myofibrils contain myofilaments that in turn are composed of Actin and Myosin. • Actin and Myosin ratio: 2:1 • Myofibrils comprise of 1500 myosin (in center) attached to 3000 actin on each side. • Portion of myofibril lying between 2 successive Z disc is Sarcomere. Myosin • Myosin has 6 polypeptide chains, 4 light chains & 2 heavy chains. • 2 heavy chains form double helix twisting forming tail. • Ends of these chain folded to form head, thereby making 2 heads lying side by side at one end of double helix myosin. Myosin • Multiple tails unite to form body with many heads handing outwards on the sides of the body with a side hanging structure called arm that helps to extend the head away from the body. • Cross bridges: Protruding arms & head together. • Cross bridges are flexible at two points called hinges. • 1. Origin of arm from body • 2. Site of attachment of head to arm. Myosin • Hinged arms cause head to either extend far outward or come closer to the body. • The hinged head in turn participate in actual contraction process. • Head has ATPase enzyme cleaving ATP and thereby deriving energy needed to cause muscle contraction. Actin • Comprises of 3 proteins: Actin, Tropomyosin and Troponin • Actin twisted around each other in 2 chains like double helix structure made of F actin protein molecule, comprising of 1 active site resulting from union of 2 F actin strands. • Tropomyosin: Attached with Actin. At resting phase, Troponin-Tropomyosin complex covers 7 active sites on actin thereby preventing myosin binding and eventually muscle contraction. • Troponin: Attached with Tropomyosin. 3 subtypes. • Troponin I: Affinity for Actin. • Troponin T: Tropomyosin. • Troponin C: Calcium ions, for contraction Ca++ uncover active sites. Sliding Mechanism • At resting phase, actin molecules are distant and apart from myosin and from each other. • When contraction is needed, actin molecules are pulled closer to myosin and to each other, overlapping each other. • Occurs because cross bridges of myosin become attached to active sites on actin, pulling the actin towards sarcomere. • Changes in bands: • Shortening of I & H band • Z line brought closer to each other. • Ca++ needed to facilitate binding between actin and myosin and ATP required to liberate energy. Walk Along Theory • In presence of Ca++ ions, head from cross bridges of myosin become attached to active sites on actin causing contraction. • Walk along theory=Ratchet theory of contraction. • Constant attachment and detachment of the head from active site on actin takes place, hence myosin head moves along the next active sites on actin in a sequence. • Power stroke: The tilt of myosin head towards the arm causing dragging of the actin filament along. • Followed by detachment of the head, returning to normal position and again binding with newer active site on actin. • Fenn effect: Greater the amount of work to be performed by muscle, greater will be the amount of ATP to be cleaved. Mechanism for muscle contraction • 1. Action potential travels through motor nerve to endings on muscle fiber. • 2. At the nerve ending, Acetylcholine; neurotransmitter is released. • 3. Acetylcholine acts on Acetylcholine channels. • 4. Inflow of Na+ ions occur causing depolarization. • 5. Action potential travels through muscle fiber membrane. • 6. Sarcoplasmic reticulum releases Ca++ • 7. Ca++ inititate binding between actin and myosin. • 8. Ca++ pumped back into Sarcoplasmic reticulum hence stopping contraction. Extras • Motor unit: All the muscle fibers innervated by single motor nerve. • Muscle fatigue: Anaerobic glycolysis, lactic acid accumulation causing tissue injury. • Hypertrophy: Increase in size of the muscle fiber. • Hyperplasia: Increase in number of normal muscle fiber in normal arrangement. • Rigor Mortis: Loss of ATP after death fails to separate cross bridges from actin causing muscles to remain contracted and remain rigid. Takes 15-25 hours to resolve. http://coolbluez.t15.org