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OUTLINE 1. Skeletal Muscle Overview A. General Principles B. Structures C. Skeletal Muscle Histology D. Myofilaments E. Proteins 2. Skeletal Muscle Contraction A. Neuromuscular Junction B. Muscle Cell Depolarization C. Muscle Contraction D. Muscle Relaxation E. Malignant Hyperthermia 3. Metabolic Exercise Physiology A. ATP Sources by Time B. Type I (Red) Muscle Fibers C. Type II (White) Muscle Fibers 4. Sarcomere A. Thick Filaments B. Thin Filaments C. M Band D. H Zone E. I Band F. A Band 5. Muscle Proprioception A. Muscle Spindles B. Golgi Tendon Organ Musculoskeletal System: Skeletal Muscle
Musculoskeletal System: Skeletal Muscle Bootcamp.com General Principles: • Function: Muscle contraction or tension to resist load • Calcium required for muscle cell contraction • Striated fibers: Skeletal muscle • Nonstriated fibers: Smooth muscle • Embryologic origin: Mesoderm Structures: • Sarcolemma: Muscle cell membrane, T-tubules à Dihydropyridine receptor • Sarcoplasmic Reticulum: Muscle cell endoplasmic reticulum, stores calcium, ryanodine receptor • Sarcoplasm: Muscle cell cytoplasm Skeletal Muscle Histology: • Multinucleated, striated, nuclei located in periphery Myofilaments: • Actin: Thin filament • Myosin: Thick filament, binding site for actin and ATP (ATPase activity) • Slide along actin filament via ATP hydrolysis Proteins: • Tropomyosin: Blocks myosin binding on actin • Troponin C: Activated by Ca2+ à Conformational change in tropomyosin
Bootcamp.com Neuromuscular Junction: • Depolarization transmission down axon à ↑ Voltage-gated Ca2+ channel opening à ↑ Ca2+ into axon • Calcium-induced ACh vesicle exocytosis à ACh binds to AChR on motor end-plate à Ligand-gated Na+ channel opening Muscle Cell Depolarization: • ↑ Na+ into sarcoplasm à Depolarization of muscle cell à Travels down T-tubule • Depolarization of DHPRà Mechanical coupling to RYR • Opening of ryanodine receptor à ↑ Ca2+ into sarcoplasm Muscle Contraction: • Ca2+ binds troponin C à Exposes binding site on actin for myosin to bind • Myosin performs ‘power stroke’ releasing Pi and ADP • Myosin binds ATP à Myosin detaches from actin à ATP is hydrolyzed to ADP (process repeats if Ca2+ present) Muscle Relaxation: • SERCA pumps calcium into sarcoplasmic reticulum via ATP à ↓ Ca2+ in sarcoplasm • Tropomyosin blocks myosin binding site due to ↓ Ca2+ Malignant Hyperthermia: • AD (usually) ryanodine receptor mutations (RYR-1) • Volatile anesthetics, succinylcholine are classic causes • Continuous opening of ryanodine receptor à ↑↑↑ Ca2+ into sarcoplasm • ↑ ATP requirements à O2 consumption, ↑ CO2 production à Myonecrosis • Lactic acidosis, hyperkalemia, hyperthermia, hypercatabolic state, rhabdomyolysis • Caffeine-Halothane contracture test • Management with dantrolene and cooling measures Musculoskeletal System: Skeletal Muscle Point here being that all skeletal muscle fibers must be stimulated individually at their motor tropomyosin complex to actin and troponin C contains binding

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