P.R. Smith, Cell Biology Skeletal Muscle Control
P.R. Smith, Cell Biology
from Gray’s Anatomy
P.R. Smith, Cell Biology Neuromuscular Junctions Motor Nerve
P.R. Smith, Cell Biology Junctional folds Nerve Terminal S
P.R. Smith, Cell Biology
Kessel/Kardon
P.R. Smith, Cell Biology T-tubule Terminal Cisterna Calsequestrin Ryanodine receptor Dihydropyridine receptor Ryanodine receptor
P.R. Smith, Cell Biology T-tubule Lumen Muscle sarcoplasm VV Ca 2+ T-T TC/SR Dihydropyridine receptor Ryanodine receptor Calsequestrin calcium ATPase
P.R. Smith, Cell Biology
Actin-Myosin Force-Generating Interaction Regulated by troponin-tropomyosin 1.[Ca ++ ].LT M -- ATPase inhibited ( no cross-bridge cycling) 2.[Ca ++ ].GT M -- ATPase not inhibited Typical of striated muscle.
P.R. Smith, Cell Biology
Actin-Myosin Interaction Cross-Bridge Cycling
P.R. Smith, Cell Biology One Half of the Myosin Molecule
P.R. Smith, Cell Biology Myosin Dimer
P.R. Smith, Cell Biology Skeletal Muscle Thick Filament
P.R. Smith, Cell Biology Woodhead el al. (2005) Nature,
P.R. Smith, Cell Biology
(Kabsch et al. 1990)
P.R. Smith, Cell Biology Visualizing Troponin In porcine cardiac muscle Spiess et al. (1999) JSB, 126,
P.R. Smith, Cell Biology Myosin Tropomyosin Actin Metzger & Westfal, 2004 Troponin Complex (T,I,C) cf: Ross, p252
P.R. Smith, Cell Biology
Actin-Stimulated ATPase Activity - Actin : active - Actin + Trop : active - Actin + Trop + T T + T I : inhibited - Actin + Trop + T T + T I + T C : [Ca ++ ] regulated } [Ca ++ ] ind.
P.R. Smith, Cell Biology Metzger & Westfal, 2004 Myosin S1
P.R. Smith, Cell Biology Vale, Milligan and Johnson, 2000
P.R. Smith, Cell Biology Mann/mann14.html
P.R. Smith, Cell Biology Cardiac Muscle
P.R. Smith, Cell Biology
from Gray’s Anatomy
P.R. Smith, Cell Biology Smooth Muscle
P.R. Smith, Cell Biology
Sarcoplasmic Matrix
P.R. Smith, Cell Biology Smooth Muscle Contraction Occurs in response to:- Nerve stimulation (autonomic) Mechanical stretching Hormones / Drugs
P.R. Smith, Cell Biology Smooth Muscle Thin Filaments Thin filaments contain actin with tropomyosin, similar to striated muscle, BUT … 1. Different actin isoforms ( -vascular and -enteric vs. -skeletal, -cardiac, and -vascular; -cytoplasmic; and -cytoplasmic) 2. No troponin 3. Caldesmon 4. Calponin } Actin-based regulation?
P.R. Smith, Cell Biology A. F-actin B. F-actin + calponin C. F-actin + tropomyosin D. F-actin + trop. + calp. F-actinF-actin + calponin Hodgkinson, et al., J. Mol. Biol. (1997) 273,
P.R. Smith, Cell Biology Smooth Muscle Thick Filaments Skeletal Muscle
P.R. Smith, Cell Biology Myosin-Based Regulation of ATPase Activity Two-step process: 1.Ca ++ -dependent kinase activated ([Ca ++ ] ≈ ) 2.Kinase phosphorylates myosin light chains: contraction 3.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.
P.R. Smith, Cell Biology Myosin-Based Regulation of ATPase Activity MLCK - myosin light chain kinase CM - Calmodulin
P.R. Smith, Cell Biology Actin Filament Attachment
P.R. Smith, Cell Biology Smooth Muscle Contraction S.J. Gunst, et al., 2003
P.R. Smith, Cell Biology The End!
P.R. Smith, Cell Biology Actin-Based Regulation of ATPase Activity Regulated by presence of troponin-tropomyosin: 1.[Ca ++ ].LT M -- ATPase inhibited ( no cross-bridge cycling) 2.[Ca ++ ].GT M -- ATPase not inhibited The actin-stimulated myosin ATPase is inhibited if the myosin light chains are not phosphorylated. Typical of smooth muscle.
P.R. Smith, Cell Biology Smooth Muscle Functionally - Two types: 1.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) 2.Single-unit / unitary (e.g. visceral) Spontaneous contractions (peristalsis) Many intercellular connections Characteristics: Cells typically small & spindle- shaped; central nucleus; “Smooth” appearance (no striations); Involuntary;