Skeletal Muscle Physiology Part One PDF

Physiology of Skeletal Muscle Fac. of Health Sciences Istanbul Atlas University Istanbul Sept. 2024  Learning outcomes Muscle Functions Muscle Characteristics Skeletal Muscle Physiology Functional Anatomy Physiology of muscle contra...

Physiology of Skeletal Muscle Fac. of Health Sciences Istanbul Atlas University Istanbul Sept. 2024  Learning outcomes Muscle Functions Muscle Characteristics Skeletal Muscle Physiology Functional Anatomy Physiology of muscle contraction Skeletal Muscle Types Energy sources and metabolism Adaptive Responses,…  Skeletal Muscle  Muscle fiber : Long cylindrical cells Many nuclei per cell (multinucleated) ( Nuclei are peripherally located ) Striated Voluntary and involuntary (reflexes) Rapid contractions Skeletal muscles are voluntary muscles, controlled by nerves of the central nervous system Motor neurons  stimulate muscle fibers to contract  Neuron axons branch so that each muscle fiber* (muscle cell) is innervated.  Form a neuromuscular junction Organization of Skeletal Muscle  Functional anatomy of Muscle Fiber  Sarcolemma : cell membrane  Surrounds the sarcoplasm (cytoplasm of fiber) Contains many of the same organelles seen in other cells An abundance of the oxygen-binding protein myoglobin  Punctuated by openings called the transverse tubules (T-tubules) Narrow tubes that extend into the sarcoplasm at right angles to the surface Filled with extracellular fluid  Functional anatomy of Muscle Fiber  Myofibrils :cylindrical structures within muscle fiber  Are bundles of protein filaments (myofilaments) Two types of myofilaments : 1. Actin filaments (thin filaments) 2. Myosin filaments (thick filaments)  At each end of the fiber, myofibrils are anchored to the inner surface of the sarcolemma  When myofibril shortens, muscle shortens (contracts)  Sarcoplasmic Reticulum (SR)  SR runs longitudinally and surrounds each myofibril Form chambers called terminal cisternae on either side of the T-tubules A single T-tubule and the 2 terminal cisternae form a triad  SR stores Ca+2 when muscle not contracting When stimulated*, calcium released into sarcoplasm SR membrane has Ca+2 pumps that function to pump Ca+2 out of the sarcoplasm back into the SR after contraction Ultrastructure of Muscle  Transverse Tubules (T tubules)  Transmit action potential : impulses through cell  Allow entire muscle fiber to contract simultaneously  Have same properties as sarcolemma Sarcomere components  Sarcomere (Z Disk to Z Disk)  Sarcomere : functional units of a myofibril About 10,000 sarcomeres per myofibril, end to end Each is about 2 µm long  Z disk: filamentous network of protein. Serves as attachment for actin myofilaments  Differences in size, density, and distribution of thick and thin filaments gives the muscle fiber a banded or striated appearance.  Cont.  A bands: a dark band; full length of thick (myosin) filament  M line - protein to which myosin attach  H zone - thick but NO thin filaments  I bands: a light band; from Z disks to ends of thick filaments Thin but NO thick filaments Extends from A band of one sarcomere to A band of the next sarcomere  Actin (Thin) Myofilaments  Thin Filament: composed of 3 major proteins* F (fibrous) actin Tropomyosin Troponin  Two strands of fibrous (F) actin form a double helix extending the length of the myofilament; attached at either end at sarcomere.  Composed of G actin monomers each of which has a myosin-binding site  Actin site can bind myosin during muscle contraction.  Tropomyosin: an elongated protein winds along the groove of the F actin double helix.  Troponin is composed of three subunits  Troponin Complex Tn I : bound to the actin fiber and is inhibitory, by blocking the binding site Tn T : bound to the tropomyosin fiber holding it in place Tn C : will bind to Ca++ ions to cause a position shift that exposes the actin binding site so that cross-bridging can occur, resulting in contraction.  Myosin (Thick) Myofilament Many elongated myosin molecules shaped like golf clubs. Single filament contains roughly 300 myosin molecules Molecule consists of two heavy myosin molecules wound together to form a rod portion lying parallel to the myosin myofilament and two heads that extend laterally.  Myosin heads  Can bind to active sites on the actin molecules to form cross-bridges. (Actin binding site)  Attached to the rod portion by a hinge region that can bend and straighten during contraction.  Have ATPase activity: activity that breaks down adenosine triphosphate (ATP), releasing energy. Part of the energy is used to bend the hinge region of the myosin molecule during contraction. Cont. Myofilaments: Banding Pattern  Four Thin Filaments F actin: is 2 twisted rows of globular G actin the active sites on G actin strands bind to myosin Nebulin: holds F actin strands together Tropomyosin: is a double strand prevents actin–myosin interaction Troponin: a globular protein binds tropomyosin to G actin controlled by Ca2+  Sarcomere Function  Transverse tubules encircle the sarcomere near zones of overlap. Ca2+ released by SR causes thin and thick filaments to interact. Muscle Contraction : is caused by interactions of thick and thin filaments. Structures of protein molecules determine interactions.  Skeletal Muscle Contraction  Skeletal muscle must: Be stimulated by a nerve ending Propagate an electrical current, or action potential, along its sarcolemma Have a rise in intracellular Ca2+ levels, the final trigger for contraction Linking the electrical signal to the contraction is excitation-contraction coupling  1.Neuromuscular Junction (NMJ)  The neuromuscular junction is formed from:  Axonal endings, which have small membranous sacs (synaptic vesicles) that contain the neurotransmitter acetylcholine (ACh)  The motor end plate of a muscle, which is a specific part of the sarcolemma that contains ACh receptors and helps form the neuromuscular junction  NMJ  When a nerve impulse reaches the end of an axon at the neuromuscular junction: Voltage-regulated calcium channels open and allow Ca2+ to enter the axon Ca2+ inside the axon terminal causes axonal vesicles to fuse with the axonal membrane  Action Potential This fusion releases ACh into the synaptic cleft via exocytosis ACh diffuses across the synaptic cleft to ACh receptors on the sarcolemma Binding of ACh to its receptors initiates an action potential in the muscle  Depolarization  A transient depolarization event that includes polarity reversal of a sarcolemma (or nerve cell membrane) and the propagation of an action potential along the membrane.  Later, an action potential spreads in all directions across the sarcolemma  Cont. ACh bound to ACh receptors is quickly destroyed by the enzyme acetyl cholinesterase. This destruction prevents continued muscle fiber contraction in the absence of additional stimuli.  2.Excitation-Contraction (E-C) Coupling  AP along sarcolemma and through T-Tubule to Triads  AP cross Terminal Cisternae of SR : releases Ca+2 into sarcoplasm – to microfilaments  Ca+2 binds to Troponin (TnC) and alters shape : exposes Actin binding sites  Sliding Filament Theory 1. Action potential travels to sarcoplasmic reticulum and releases calcium ions into sarcoplasm 2. Calcium ions bind with troponin, moving aside tropomyosin protein strands covering binding sites on actin filament 3. Myosin heads are charged with energy from breakdown of ATP 4. Energy binds myosin heads to active receptor sites on actin filament, making connections called cross-bridges 5. Ratcheting action (power stroke) occurs as myosin heads pull sarcomere together, shortening the strand 6. Myosin heads bind more ATP, providing energy needed to release hold on actins strand; process creates contractions.  Cont.  Cross bridge attachment: The activated myosin heads are attracted to the exposed binding sites on actin and cross bridge attachment occurs.  Power stroke : The sliding action , which occurs at the same time for thousands of actin and myosin molecules is referred to as the power stroke  3. Contraction-Relaxation Cycle  Myosin upon attaching to actin is hydrolyzed (phosphate coming from the splitting of ATP by Myosin ATPase)  This changes the conformation of myosin causing it to bend at the neck towards the M-line  Cont.  ADP is released by the conformational change during the “power stroke”  ATP binding site is now available for another ATP  Splitting of ATP to ADP + P by myosin detaches and returns myosin to its active state  This single event creates a twitch. THANK YOU