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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
Neuromuscular Junctions Motor Nerve
Junctional folds S Nerve Terminal
Terminal Cisterna T-tubule Dihydropyridine receptor Ryanodine receptor Calsequestrin Ryanodine receptor Terminal Cisterna
T-tubule Lumen Dihydropyridine receptor V T-T Muscle sarcoplasm Ryanodine receptor Ca2+ TC/SR Ca2+ calcium ATPase Calsequestrin
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.
1 4 3 2
Actin-Myosin Interaction Cross-Bridge Cycling
Visualizing Troponin In porcine cardiac muscle Spiess et al. (1999) JSB, 126, 98-104
Troponin Complex (T,I,C) Myosin Actin Tropomyosin cf: Ross, p252 Metzger & Westfal, 2004
Actin-Stimulated ATPase Activity • Actin : active • Actin + Trop : active • Actin + Trop + TT + TI : inhibited • Actin + Trop + TT + TI + TC : [Ca++] regulated } [Ca++] ind.
Myosin S1 Metzger & Westfal, 2004
Smooth Muscle Contraction • Occurs in response to:- • Nerve stimulation (autonomic) • Mechanical stretching • Hormones / Drugs
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
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
Skeletal Muscle Smooth Muscle Thick Filaments
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.
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
Smooth Muscle Contraction S.J. Gunst, et al., 2003
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.
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