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Chapter 2-2

Chapter 2-2

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Chapter 2-2

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  1. Chapter 2-2 THE MUSCLE AND ITS CONTRACTION

  2. the Neuromuscular Junction (NMJ)

  3. Skeletal Muscle Innervation

  4. Illustration of the Neuromuscular Junction (NMJ)

  5. New Ion Channel Players • Voltage-gated Ca2+ channel • in presynaptic突触前的 nerve terminal • mediates neurotransmitter release • Nicotinic Acetylcholine乙酰胆碱 Receptor Channel • in muscle neuromuscular junction (postsynaptic突触后的 membrane, or end plate) • mediates electrical transmission from nerve to muscle

  6. Nerve Terminal Ca2+ channels • Structurally similar to Na+ channels • Functionally similar to Na+ channels except • activation occurs at more positive potentials • activation and inactivation much slower than Na+ channels

  7. Neuromuscular Transmission Myelin Axon Axon Terminal Skeletal Muscle

  8. - - + + + - - + - + - + - + + + - Look here + - + - + Neuromuscular Transmission: Step by Step Depolarization去极化 of terminal opens Ca channels Nerve action potential invades axon terminal

  9. ACh is released and Diffuses扩散 across synaptic cleft. Ca2+ induces fusion熔合 of vesicles with nerve terminal membrane. ACh ACh Ca2+ ACh Ca2+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ ACh Na+ Na+ Na+ Na+ Na+ Na+ Na+ Nerve terminal Binding of ACh opens channel pore that is permeable to Na+ and K+. K+ K+ K+ K+ K+ Outside Muscle membrane Inside ACh binds to its receptor on the postsynaptic membrane K+ K+ K+ K+ K+ K+ K+ K+

  10. EPP End Plate Potential (EPP) VNa The movement of Na+ and K+ depolarizes muscle membrane potential (EPP) 0 Muscle Membrane Voltage (mV) Threshold Presynaptic terminal -90 mV VK Time (msec) Presynaptic AP Outside Muscle membrane Inside Voltage-gated Na Channels ACh Receptor Channels Inward Rectifier K Channels

  11. Structural Reality

  12. Neuromuscular Transmission • Properties特性 of neuromuscular junction • 1:1 transmission: A chemical transmission which is designed to assure that every presynaptic action potential results in a postsynaptic one • An unidirectional单向性 process • Has a time delay. 20nm/0.5-1ms • Is easily affect by drugs and some factors • The NMJ is a site of considerable clinical importance

  13. NMJ Diseases • Myasthenia Gravis (重症肌无力) • Autoimmunity to ACh receptor • Fewer functional ACh receptors • Low “safety factor” for NM transmission • Lambert-Eaton syndrome(兰伯特-伊顿综合征 ,癌性肌无力综合征 ) • Autoimmunity directed against Ca2+channels • Reduced ACh release • Low “safety factor” for NM transmission

  14. Microstructure of Skeletal Muscle

  15. Skeletal Muscle • Human body contains over 400 skeletal muscles • 40-50% of total body weight • Functions of skeletal muscle • Force production for locomotion运动 and breathing • Force production for postural姿势 support • Heat production during cold stress

  16. Fascicles肌束: bundles, CT(connective tissue结缔组织) covering on each one • Muscle fibers: muscle cells

  17. Structure of Skeletal Muscle:Microstructure • Sarcolemma(肌管系统) • Transverse (T) tubule • Longitudinal tubule (Sarcoplasmic reticulum, SR肌浆网) • Myofibrils(肌原纤维) • Actin肌动蛋白 (thin filament) • Troponin(肌钙蛋白) • Tropomyosin(原肌球蛋白) • Myosin肌球蛋白 (thick filament)

  18. Within the sarcoplasm Triad (三联管) • Transverse tubules • Sarcoplasmic reticulum -Storage sites for calcium • Terminal cisternae - Storage sites for calcium

  19. Microstructure of Skeletal Muscle (myofibril)

  20. Sarcomeres • Sarcomere 肌小节: bundle of alternating thick and thin filaments • Sarcomeres join end to end to form myofibrils • Thousands per fiber, depending on length of muscle • Alternating thick and thin filaments create appearance of striations条痕

  21. Myosin 肌球蛋白 • Myosin head is hinged铰链 • Bends and straightens during contraction

  22. Thick filaments (myosin) • Bundle of myosin proteins shaped like double-headed golf clubs • Myosin heads have two binding sites • Actin binding site forms cross bridge • Nucleotide核苷酸 binding site binds ATP (Myosin ATPase) • Hydrolysis水解 of ATP provides energy to generate power stroke

  23. Thin filaments 原肌球蛋白 肌钙蛋白 肌动蛋白

  24. Thin filaments (actin) • Backbone: two strands of polymerizedglobular actin – fibrous actin • Each actin has myosin binding site • Troponin • Binds Ca2+; regulates muscle contraction • Tropomyosin • Lies in groove of actin helix • Blocks myosin binding • sites in absence of Ca2+

  25. Thick filament: Myosin (head and tail) • Thin filament: Actin, Tropomyosin, Troponin (calcium binding site)