1. Muscle Physiology

2. 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

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

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

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

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

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

8. Depolarization of Muscle Cell Resting Depolarization Repolarization Resting Depolarization 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 Bone Tendon Muscle Muscle Fascicle Muscle Fiber Myofibril Myosin Actin Myofibrils contain the contractile mechanism of skeletal muscle

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

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? Fascicle Sacrolemna Muscular Dystrophy = NO DYSTOPHIN!

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

16. Actin: Activation TropomyosinTroponinActin REST: active sites are not exposed ACTIVATION: Ca 2+ binds to Troponin Exposing active sites Active Site

17. Where does Ca 2+ come from? Sarcoplasmic Reticulum T-tubules Sacrolemna Muscle Fiber

18. Calcium initiates muscle contraction: Where does Ca 2+ come from in Skeletal Muscle? Sarcoplasmic reticulum RyR T-tubule Ca 2+ Stores 1 Myosin Actin DHP: VG-Ca2+ RyR = Ryanodine Receptor-channel DHP = Dihydropyridine Ca2+ channel

19. Sarcoplasmic reticulum RyR Ca 2+ EFFLUX Myosin Actin DHP: VG-Ca2+ RyR = Ryanodine Receptor-channel DHP = Dihydropyridine Ca2+ Receptors Skeletal Muscle: Calcium Efflux from SR

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

21. Cross-bridge Cycling: Striated & Smooth Muscle 12345 1)Cross-bridge Formation Myosin head: loaded with potential energy Myosin Actin PiPi ADP

22. Cross-bridge Cycling: Striated & Smooth Muscle 12345 2) Power Stroke: Phosphate release Stored Potential Energy is released Myosin PiPi ADP Actin SLIDES

23. Cross-bridge Cycling: Striated & Smooth Muscle 12345 3) ADP dissociation Myosin Actin ADP

24. Cross-bridge Cycling: Striated & Smooth Muscle 12345 4) Rigor State Myosin Actin

25. Cross-bridge Cycling: Striated & Smooth Muscle 12345 5) NEW ATP Binding: Myosin detaches Myosin Actin ATP Rigor Mortis

26. Myosin Cocking (between steps 5 & 1) 12345 ATP + H 2 0 ADP + P i + H + + ENERGY Hydrolysis by Myosin ATPase Myosin Cocking Once Cocked the Myosin head is loaded with POTENTIAL ENERGY

27. 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

28. How muscles RELAX Sarcoplasmic Reticulum T-tubules Sacrolemna Muscle Fiber 1)Action Potential move along Sacrolemna 2)Action Potenial penetrates T-tubules & SR 3)VG Ca 2+ in SR open, releasing Ca 2+ onto Sarcomeres 4)Ca 2+ binds to Troponin, exposing Actin’s active sites 5)Actin Binds to Myosin 1)Acetylcholine detaches from Na+ channels at Neuromuscular junction 2)Ca2+ is pumped (by Ca2+ ATPase pump!) back into Sacroplasmic Reticulum

29. Return to resting position : Titin Myosin Actin Sarcomere Z-disk Cross-bridges http://www.fbs.leeds.ac.uk/research/contractility/titin.htm 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 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 Muscle fiber was not able to relax so tension increased Summation occurs because Ca2+ is still bound to actin 2 nd 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 TYPE 1 TYPE 2B TYPE 2A Fiber type is the same within a Motor Unit!!!!!!!!!!!!!!!!!!!!!! WHITE MUSCLE RED MUSCLE

39. WildType = normal ratTransGenic = 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 Maximum Running Distance Maximum Running Speed 100 m Dash olympian – Type 2B 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? Aerobic Respiration Anaerobic Respiration Creatine 10 seconds 3 minutesHours