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Muscle Physiology Outline: Skeletal Muscle 1) Somatic Motor pathways 2) Neuromuscular junction (synapse) 3) Excitation of muscle cells 4) Contraction of muscle cells 5) Neural modulation of excitation-contraction 6) Variation in Skeletal muscle physiology 7) Energy sources for contraction 8) Effects of fatigue and exercise Somatic Motor Pathways Primary Motor Cortex Indirect Pathways: Direct Pathways: Posture Positioning Coordination Fine Motor Control Muscle Tone Brainstem Skeletal Muscle Indirect Pathways: Direct Pathways: Posture Positioning Coordination Fine Motor Control Muscle Tone Many muscles receive input from both pathways Cerebellum: Coordination of Motor Output Spinocerebellar Primary Motor Cortex Simple Movements Cerebrocerebellar Complex movements Vestibulocerebellar Posture & Balance Motor Commands Sensory feedback from proprioreceptors (muscle spindle and golgi organ) Neuromuscular Junction Chemical synapse between Motor Neurons and Muscle Cells Neuromuscular junction: Physiology 1) Action potential from Motor Neuron 1 2) VG Ca2+ channels open 2 3) Ca2+ influx 3 4) Vesicles of ACh release to synaptic cleft 4 7 5 6 5) ACh binds to ligand-gated Na+ channels on Muscle membrane 6) Na+ influx 7) Depolarization of Muscle cell EXCITABLE MEMBRANE Depolarization of Muscle Cell Resting Depolarization Resting Repolarization Everything about muscle cell action potentials is identical to neurons (All-or-none, etc)! Exception: RMP = -85 mV So you have an excited muscle cell membrane…… Excitation of the muscle cell membrane leads to muscle cell contraction via a mechanism called: Excitation-Contraction Coupling Muscle microanatomy Muscle Fascicle Muscle Fiber Muscle Tendon Bone Actin Myosin Myofibril Myofibrils contain the contractile mechanism of skeletal muscle Functional organization of Myofibril: The Sacromere Sarcomere Actin Myosin Z-disk Cross-bridges Z-disk Sliding Filament Model: Contraction Relaxed Muscle: large gap between actins Resting Position of Z-disc Contraction: gap between actins NARROWS Maximal contraction: NO gap between actins Sliding Filament Model: Generalizations Actin & Myosin do not change length Only Actin moves Each Sacromere shortens VERY LITTLE Relaxation is passive How do sliding filaments result in whole muscle shortening and force? Muscular Dystrophy = NO DYSTOPHIN! Fascicle Sacrolemna Cross-Bridge Cycling : Mechanism of Sliding Filaments Sarcomere Cross-bridges Actin Myosin Z-disk Z-disk Actin: Activation Active Site Tropomyosin Actin Troponin REST: active sites are not exposed ACTIVATION: Ca2+ binds to Troponin Exposing active sites Where does Ca2+ come from? T-tubules Sarcoplasmic Reticulum Sacrolemna Muscle Fiber Calcium initiates muscle contraction: Where does Ca2+ come from in Skeletal Muscle? 1 RyR T-tubule Ca2+ Stores DHP: VG-Ca2+ Sarcoplasmic reticulum Actin Myosin RyR = Ryanodine Receptor-channel DHP = Dihydropyridine Ca2+ channel Skeletal Muscle: Calcium Efflux from SR RyR DHP: VG-Ca2+ Ca2+ EFFLUX Sarcoplasmic reticulum Actin Myosin RyR = Ryanodine Receptor-channel DHP = Dihydropyridine Ca2+ Receptors Cross Bridge Cycling: What happens after Actin & Myosin Bind? Muscle Cross Bridge Video Cross-bridge Cycling: Striated & Smooth Muscle 1 2 3 Actin ADP 4 5 1) Cross-bridge Formation Pi Myosin head: loaded with potential energy Myosin Cross-bridge Cycling: Striated & Smooth Muscle 1 2 3 4 5 Actin SLIDES ADP 2) Power Stroke: Phosphate release Pi Stored Potential Energy is released Myosin Cross-bridge Cycling: Striated & Smooth Muscle 1 2 3 Actin 4 5 3) ADP dissociation ADP Myosin Cross-bridge Cycling: Striated & Smooth Muscle 1 2 3 4 4) Rigor State Actin Myosin 5 Cross-bridge Cycling: Striated & Smooth Muscle 1 2 3 4 5 5) NEW ATP Binding: Myosin detaches Actin ATP Myosin Rigor Mortis Myosin Cocking (between steps 5 & 1) 1 2 3 4 5 Hydrolysis by Myosin ATPase ATP + H20 ADP + Pi + H+ + ENERGY Myosin Cocking Once Cocked the Myosin head is loaded with POTENTIAL ENERGY Muscle Contraction: Synthesis 1) Brain send AP down Motor pathways to Neuromuscular junction 2) Neuromuscular junction propagates AP to sarcolemna 3) AP on sacrolemna propagates down t-tubules into SR 4) SR releases Ca2+; Myosin & Actin bind 5) Cross-bridge cycling; Sliding Filaments T-tubules Sarcoplasmic Reticulum 1) Action Potential move along Sacrolemna 2) Action Potenial penetrates T-tubules & SR 3) VG Ca2+ in SR open, releasing Ca2+ onto Sarcomeres 4) Ca2+ binds to Troponin, exposing Actin’s active sites Sacrolemna 5) Actin Binds to Myosin Muscle Fiber How muscles RELAX 1) Acetylcholine detaches from Na+ channels at Neuromuscular junction 2) Ca2+ is pumped (by Ca2+ ATPase pump!) back into Sacroplasmic Reticulum Return to resting position : Titin Sarcomere Cross-bridges Actin Myosin Z-disk Z-disk TITIN http://www.fbs.leeds.ac.uk/research/contractility/titin.htm Muscle Contraction lead to FORCE What do we know about MUSCLE FORCE? Tension: how muscle develop force Single MOTOR UNIT developing tension Muscle twitch: contraction of motor unit in response to a single action potential Stimulus applied Stimulus applied Stimulus applied Muscle Twitches are All-or-None! Motor Unit = a single motor neuron and all the muscle fibers it innervates Muscle force can be altered 1) WITHIN SINGLE MOTOR UNITS 2) BETWEEN MULTIPLE MOTOR UNITS Summation: Single Motor Unit Stimulus applied Stimulus applied Muscle fiber was not able to relax so tension increased Summation occurs because Ca2+ is still bound to actin 2nd AP releases MORE Ca2+ causing more actin to be exposed to myosin heads When action potentials come VERY RAPIDLY muscle fiber CANNOT relax Unfused (Incomplete) Tetanus Fused (Complete) Tetanus Summation & Tetanus allow single motor units to increase Tension (Force) Motor Unit Recruitment Different Motor Units can WORK TOGETHER to further increase force! Tension varies with the starting length of the sacromere Muscle Twitches Variation in Muscle Fibers RED MUSCLE TYPE 1 WHITE MUSCLE TYPE 2B TYPE 2A Fiber type is the same within a Motor Unit!!!!!!!!!!!!!!!!!!!!!! WildType = normal rat TransGenic = rat with more Type I TG rat has darker muscles due to more myoglobin, mitochondria Myoglobin Oxygen Fiber types & Diameter underlie the trade-off between sprinting & marathon running in Humans Maximum Running Speed 100 m Dash olympian – Type 2B Maximum Running Distance Marathon olympian – Type 1 Energy Sources for Contraction 1) ATP is needed to break cross-bridge 2) ATP > ADP + P is needed to relax Myosin head 3) P release from Myosin provides energy for Power stroke Where does the ATP come from? Creatine 10 seconds Anaerobic Respiration 3 minutes Aerobic Respiration Hours