BMS150_PHL4-01_SkelMusc1 _Win2023_2.pdf

Physiology 4.01 Skeletal Muscle Physiology I BMS 150 Week 9  Skeletal Muscle tissue Our skeletal muscles (eg. biceps) are composed of bundles of fascicles. ▪ Each fascicle is composed of linearly aligned muscle fibers (aka myofiber)...

Physiology 4.01 Skeletal Muscle Physiology I BMS 150 Week 9  Skeletal Muscle tissue Our skeletal muscles (eg. biceps) are composed of bundles of fascicles. ▪ Each fascicle is composed of linearly aligned muscle fibers (aka myofiber) The muscle fiber is a single, multi-nucleated, elongated cell Each muscle fibre is composed of many sarcomeres, arranged linearly Sarcomeres are composed of myofibrils (these are organelles) Skeletal Muscle tissue The connective tissue sheath surrounding the whole muscle and extending from the tendons is called the epimysium. ▪ The sheath surrounding each fascicle is called a perimysium. ▪ The sheath surround each individual muscle fiber is called the endomysium Below the endomysium is the sarcolemma – the cell membrane of the muscle cell. Skeletal Muscle Tissue Muscle fibers are large, multinucleated cells: Contain 1000 – 2000 myofibrils ▪ Each myofibril composed of many myofilaments, composed of: Contractile proteins ▪ Actin ▪ Myosin Regulatory proteins ▪ Tropomyosin ▪ Troponin Additional accessory proteins (FYI - actinin, dystrophin, titin, nebulin) A number of clinically-relevant disorders (i.e. muscular dystrophy) are caused by abnormalities of accessory proteins Contractile proteins - Sarcomeres Myofibrils are arranged into a series of sarcomeres, which form the contractile unit of skeletal muscle. ▪ Consist of interdigitating myofilaments, composed of: Thin filaments (made of actin) Thick filaments (made of myosin) ▪ The striated appearance of skeletal muscle is due to the overlapping of thick and thin filaments Contractile proteins - Sarcomeres Each sarcomere is bound by the Z-disk ▪ Thin filament attaches to the Z-disk ▪ Other proteins involved in stretch sensing and signal communication also attach to Z-disk. At the center is the M-line ▪ Includes a variety of proteins to bind the myosin molecules within the thick filament  Contractile proteins - Sarcomeres Thick filaments lie between and partially interdigitate with thin filaments ▪ Results in alternating light and dark bands Light bands (aka I bands) are regions of thin filaments that do not overlap with thick filaments At the center of the light bands is the Z disk Dark bands (aka A bands) are the region were the thick and thin filaments do overlap ▪ During muscle contraction, the I band shortens, while the A band does not change in length Sarcomeres - Actin Structure: Monomer: G-actin Polymer: F-actin ▪ Thin filaments are composed of two strands of F-actin wound together. ▪ Each G-actin monomer has a binding site for myosin ▪ F-actin is the major constituent of the thin filament Sarcomeres - Myosin Structure: ▪ Arranged into thick filaments composed of many myosin units. Each unit is composed of head & tail regions Head region forms cross-bridges that interact with adjacent actin filaments ▪ Many myosin units are arranged in staggered position into a thick filament Sarcomeres – Myosin: closer look Myosin head region, has 3 important biochemical features: ▪ ATPase activity ▪ Actin-binding region ▪ ATP binding region Regulatory Protein - Tropomyosin Tropomyosin is a regulatory protein that associates with actin ▪ When a skeletal muscle is in a relaxed state, tropomyosin molecules cover the myosin-binding site on G-actin monomers This prevents cross-bridge formation between actin and myosin Tropomyosin Regulatory Protein - Troponin Troponin is another regulatory protein that associates with actin. ▪ Forms a complex with 3 subunits: Troponin I, Troponin T, and Troponin C. Troponin C - binds to Calcium Troponin Troponin T - binds to Tropomyosin Troponin I – binds to actin and inhibits contraction  Regulatory Protein - Troponin Troponin continued: ▪ Function: When calcium binds to Troponin C, The troponin complex undergoes a conformational change and Troponin T “pulls” tropomyosin and Troponin I off of the myosin-binding site of G-actin subunits. ▪ This allows cross-bridge formation to occur Sarcolemma The plasma membrane of the muscle fiber is called the sarcolemma ▪ Contains invaginations called transverse Tubules (aka T- tubules) Allows the action potential to be carried deep into the muscle fiber Continuous with the extracellular fluid  Sarcolemma - continued Sarcolemma continued ▪ The sarcolemma and T-tubules closely associate with the sarcoplasmic reticulum (SR) Sarcoplasmic reticulum is a specialized endoplasmic reticulum containing high concentrations of calcium Terminal cisternae of the sarcoplasmic reticulum are specialized regions that associate with the T-tubules Muscle triad The junction between T-tubules and sarcoplasmic reticulum cisterna is called the muscle triad ▪ Volume of T-tubule is large compared to the SR cisterna ▪ Review – is the concentration of calcium in the extracellular fluid high or low?  Neuro-muscular junction A motor nerve axon contacts Motor nerve each muscle fiber near the middle of the fiber, forming a synapse called the neuromuscular junction. ▪ The region of the sarcolemma in closest contact with the presynaptic nerve terminal is called the motor end plate. Neuromuscular junction The motor nerve terminal Motor nerve releases acetylcholine (Ach), which binds to the nicotinic receptor on the sarcolemma. ▪ This gives rise to a graded, Ach depolarizing end-plate potential. ▪ Activates voltage-gated sodium channels → triggering an action potential that propagates along the sarcolemma ▪ The skeletal muscle fibre action potential “looks” very similar to the neuron action potential (slightly longer duration, ~ 10 msec) Action potential propagation The action potential propagates along the surface of the skeletal muscle fiber and penetrate deeper into the muscle fiber via the T-tubules ▪ This is the purpose of the T- tubule – to “bring” the action potential (travels along the sarcolemma) deep within the very large muscle fibres ▪ The action potential then signals to the sarcoplasmic reticulum Excitation-contraction (EC) coupling – muscle triad Action potential propagate along the T tubules and activate L-type Ca2+ channels in the sarcolemma Activation of the L-type Ca2+ channels also triggers mechanical activation of Ryanodine receptors (RYR) on the surface of the SR terminal cisterna within the cell Ryanodine receptor EC coupling - Calcium Opening of L-type Ca2+ channels and RYR allows Ca2+ to flow down its concentration gradient into the cytosol of the muscle fiber ▪ Calcium then binds to troponin (C subunit) to expose the binding sites for myosin Most of the calcium that activates the skeletal muscle sarcomere is from the SR, NOT the extracellular fluid Whole muscle contraction Typical muscle receives input from ~ 100 alpha-motor neurons ▪ The number of muscle fibers that each motor neuron innervates varies widely All the muscle fibers innervated by a single nerve fiber is called a motor unit ▪ Review: What is the alpha-motor neuron-muscle fiber complex called? ▪ Often these complexes intermingle extensively Allows motor units to contract in support of one another rather than entirely individually Twitch vs. tetany? A single action potential from a motor neuron barely causes any force development in the group of muscle fibres (motor unit) that it innervates ▪ Smooth, continuous, forceful contractions occur when the alpha-motor neuron sends many action potentials to a motor unit at a relatively high frequency Twitch vs. tetany? Tetany = development of force (tension) in a muscle fibre due to many action potentials → greater and greater release of calcium from the SR ▪ Fused tetany → maximal force development in the muscle fibres of a motor unit – no individual “twitches” visible ▪ Muscle has no time to “clear” calcium back to the SR FYI - Individual “twitch times” vary depending on role of the muscle