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Skeletal Muscle Control

Skeletal Muscle Control. from Gray’s Anatomy. Neuromuscular Junctions. Motor Nerve. Junctional folds. S. Nerve Terminal. Kessel/Kardon. Terminal Cisterna. T-tubule. Dihydropyridine receptor. Ryanodine receptor. Calsequestrin. Ryanodine receptor. Terminal Cisterna. T-tubule

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Skeletal Muscle Control

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  1. Skeletal Muscle Control

  2. from Gray’s Anatomy

  3. Neuromuscular Junctions Motor Nerve

  4. Junctional folds S Nerve Terminal

  5. Kessel/Kardon

  6. Terminal Cisterna T-tubule Dihydropyridine receptor Ryanodine receptor Calsequestrin Ryanodine receptor Terminal Cisterna

  7. T-tubule Lumen Dihydropyridine receptor V T-T Muscle sarcoplasm Ryanodine receptor Ca2+ TC/SR Ca2+ calcium ATPase Calsequestrin

  8. Actin-Myosin Force-Generating Interaction Regulated by troponin-tropomyosin [Ca++] .LT. 10-7M -- ATPase inhibited (no cross-bridge cycling) [Ca++] .GT. 10-5M -- ATPase not inhibited Typical of striated muscle.

  9. 1 4 3 2

  10. Actin-Myosin Interaction Cross-Bridge Cycling

  11. One Half of the Myosin Molecule

  12. Myosin Dimer

  13. Skeletal Muscle Thick Filament

  14. Woodhead el al. (2005) Nature, 436 1195

  15. (Kabsch et al. 1990)

  16. Visualizing Troponin In porcine cardiac muscle Spiess et al. (1999) JSB, 126, 98-104

  17. Troponin Complex (T,I,C) Myosin Actin Tropomyosin cf: Ross, p252 Metzger & Westfal, 2004

  18. Actin-Stimulated ATPase Activity • Actin : active • Actin + Trop : active • Actin + Trop + TT + TI : inhibited • Actin + Trop + TT + TI + TC : [Ca++] regulated } [Ca++] ind.

  19. Myosin S1 Metzger & Westfal, 2004

  20. Vale, Milligan and Johnson, 2000

  21. http://www.unmc.edu/Physiology/ Mann/mann14.html

  22. Cardiac Muscle

  23. from Gray’s Anatomy

  24. Smooth Muscle

  25. Sarcoplasmic Matrix

  26. Smooth Muscle Contraction • Occurs in response to:- • Nerve stimulation (autonomic) • Mechanical stretching • Hormones / Drugs

  27. Thin filaments contain actin with tropomyosin, similar to striated muscle,BUT … Different actin isoforms (-vascular and -enteric vs. -skeletal, -cardiac, and -vascular; -cytoplasmic; and -cytoplasmic) No troponin Caldesmon Calponin } Actin-based regulation? Smooth Muscle Thin Filaments

  28. F-actin F-actin + calponin A. F-actin B. F-actin + calponin C. F-actin + tropomyosin D. F-actin + trop. + calp. Hodgkinson, et al., J. Mol. Biol. (1997) 273, 150-159

  29. Skeletal Muscle Smooth Muscle Thick Filaments

  30. Myosin-Based Regulation of ATPase Activity Two-step process: Ca++-dependent kinase activated ([Ca++] ≈ 10-5) Kinase phosphorylates myosin light chains:   contraction MLC phosphatase de-phosphorilates the MLC: relaxation The actin-stimulated myosin ATPase is inhibited If the myosin light chains are not phosphorylated. Typical of smooth muscle.

  31. Myosin-Based Regulation of ATPase Activity MLCK - myosin light chain kinase CM - Calmodulin http://www.lib.mcg.edu/edu/eshuphysio/program/section2/2ch8/myosin.htm

  32. Actin Filament Attachment

  33. Smooth Muscle Contraction S.J. Gunst, et al., 2003

  34. The End!

  35. Actin-Based Regulation of ATPase Activity Regulated by presence of troponin-tropomyosin: [Ca++] .LT. 10-7M -- ATPase inhibited (no cross-bridge cycling) [Ca++] .GT. 10-5M -- ATPase not inhibited The actin-stimulated myosin ATPase is inhibited if the myosin light chains are not phosphorylated. Typical of smooth muscle.

  36. Smooth Muscle Characteristics: Cells typically small & spindle-shaped; central nucleus; “Smooth” appearance (no striations); Involuntary; • Functionally - Two types: • Multi-unit (e.g. papillary muscle in the eye, large blood vessel walls): • Under nervous control (autonomic) • Normally no spontaneous contractions • No intercellular connections (gap junctions) • Single-unit / unitary (e.g. visceral) • Spontaneous contractions (peristalsis) • Many intercellular connections

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