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Muscle Physiology

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  1. Muscle Physiology

  2. Outline: Skeletal Muscle • Somatic Motor pathways • Neuromuscular junction (synapse) • Excitation of muscle cells • Contraction of muscle cells • Neural modulation of excitation-contraction • Variation in Skeletal muscle physiology • Energy sources for contraction • Effects of fatigue and exercise

  3. Somatic Motor Pathways Primary Motor Cortex Indirect Pathways: Posture Positioning Coordination Direct Pathways: Fine Motor Control Muscle Tone Brainstem Skeletal Muscle

  4. Indirect Pathways: Posture Positioning Coordination Direct Pathways: Fine Motor Control Muscle Tone Many muscles receive input from both pathways

  5. Cerebellum: Coordination of Motor Output Spinocerebellar Simple Movements Primary Motor Cortex Cerebrocerebellar Complex movements Vestibulocerebellar Posture & Balance Sensory feedback from proprioreceptors (muscle spindle and golgi organ) Motor Commands

  6. Neuromuscular Junction Chemical synapse between Motor Neurons and Muscle Cells

  7. Neuromuscular junction: Physiology • Action potential from Motor Neuron • VG Ca2+ channels open • Ca2+ influx • Vesicles of ACh release to synaptic cleft • ACh binds to ligand-gated Na+ channels on Muscle membrane • Na+ influx • Depolarization of Muscle cell EXCITABLE MEMBRANE 1 2 3 4 7 5 6

  8. Depolarization of Muscle Cell Resting Depolarization Repolarization Depolarization Resting Repolarization Everything about muscle cell action potentials is identical to neurons (All-or-none, etc)! Exception: RMP = -85 mV

  9. 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

  10. Muscle microanatomy Muscle Fascicle Muscle Fiber Muscle Tendon Bone Actin Myofibril Myofibrils contain the contractile mechanism of skeletal muscle Myosin

  11. Functional organization of Myofibril:The Sacromere Sarcomere Actin Myosin Cross-bridges Z-disk Z-disk

  12. 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

  13. Sliding Filament Model: Generalizations Actin & Myosin do not change length Only Actin moves Each Sacromere shortens VERY LITTLE Relaxation is passive

  14. How do sliding filaments result in whole muscle shortening and force? Muscular Dystrophy = NO DYSTOPHIN! Fascicle Sacrolemna

  15. Cross-Bridge Cycling : Mechanism of Sliding Filaments Sarcomere Cross-bridges Actin Myosin Z-disk Z-disk

  16. Actin: Activation Active Site Tropomyosin Actin Troponin REST: active sites are not exposed ACTIVATION: Ca2+binds to Troponin Exposing active sites

  17. Where does Ca2+ come from? T-tubules Sarcoplasmic Reticulum Sacrolemna Muscle Fiber

  18. Calcium initiates muscle contraction:Where does Ca2+ come from in Skeletal Muscle? 1 RyR T-tubule Sarcoplasmicreticulum Ca2+ Stores DHP: VG-Ca2+ Actin Myosin RyR = Ryanodine Receptor-channel DHP = Dihydropyridine Ca2+ channel

  19. Skeletal Muscle: Calcium Efflux from SR RyR DHP: VG-Ca2+ Sarcoplasmicreticulum Ca2+ EFFLUX Actin Myosin RyR = Ryanodine Receptor-channel DHP = Dihydropyridine Ca2+ Receptors

  20. Cross Bridge Cycling: What happens after Actin & Myosin Bind? Muscle Cross Bridge Video

  21. Cross-bridge Cycling: Striated & Smooth Muscle 1 2 3 4 5 Actin ADP • Cross-bridge Formation • Myosin head: • loaded with potential energy Pi Myosin

  22. Cross-bridge Cycling: Striated & Smooth Muscle 1 2 3 4 5 Actin SLIDES ADP 2) Power Stroke: Phosphate release Stored Potential Energy is released Pi Myosin

  23. Cross-bridge Cycling: Striated & Smooth Muscle 1 2 3 4 5 Actin 3) ADP dissociation ADP Myosin

  24. Cross-bridge Cycling: Striated & Smooth Muscle 1 2 3 4 5 4) Rigor State Actin Myosin

  25. Cross-bridge Cycling: Striated & Smooth Muscle 1 2 3 4 5 5) NEW ATP Binding: Myosin detaches Actin ATP Rigor Mortis Myosin

  26. Myosin Cocking (between steps 5 & 1) 1 2 3 4 5 Hydrolysis by Myosin ATPase ADP + Pi + H+ + ENERGY ATP + H20 Myosin Cocking Once Cocked the Myosin head is loaded with POTENTIAL ENERGY

  27. Muscle Contraction: Synthesis • Brain send AP down Motor pathways to Neuromuscular junction • Neuromuscular junction propagates AP to sarcolemna • AP on sacrolemna propagates down t-tubules into SR • SR releases Ca2+; Myosin & Actin bind • Cross-bridge cycling; Sliding Filaments

  28. How muscles RELAX T-tubules • Action Potential move along Sacrolemna • Action Potenial penetrates T-tubules & SR • VG Ca2+ in SR open, releasing Ca2+ onto Sarcomeres • Ca2+ binds to Troponin, exposing Actin’s active sites • Actin Binds to Myosin Sarcoplasmic Reticulum Sacrolemna Muscle Fiber • Acetylcholine detaches from Na+ channels at Neuromuscular junction • Ca2+ is pumped (by Ca2+ ATPase pump!) back into Sacroplasmic Reticulum

  29. Return to resting position : Titin Sarcomere Cross-bridges Actin Myosin Z-disk Z-disk TITIN

  30. Muscle Contraction lead to FORCE What do we know about MUSCLE FORCE?

  31. Tension: how muscle develop force Single MOTOR UNIT developing tension

  32. 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!

  33. 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

  34. 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

  35. 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)

  36. Motor Unit Recruitment Different Motor Units can WORK TOGETHER to further increase force!

  37. Tension varies with the starting length of the sacromere Muscle Twitches

  38. Variation in Muscle Fibers RED MUSCLE TYPE 1 WHITE MUSCLE TYPE 2B TYPE 2A Fiber type is the same within a Motor Unit!!!!!!!!!!!!!!!!!!!!!!

  39. WildType = normal rat TransGenic = rat with more Type I TG rat has darker muscles due to more myoglobin, mitochondria Myoglobin Oxygen

  40. Fiber types & Diameter underlie the trade-off between sprinting & marathon running in Humans 100 m Dash olympian – Type 2B Maximum Running Speed Maximum Running Distance Marathon olympian – Type 1

  41. 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? Anaerobic Respiration Creatine Aerobic Respiration 10 seconds 3 minutes Hours