Mechanism of action of endothelin in rat cardiac muscle: cross-bridge kinetics and myosin light chain phosphorylation.
1. The molecular mechanism of inotropic action of endothelin was investigated in rat ventricular muscle by studying its effects on characteristics of isometric twitch, barium-induced steady contracture and the level of incorporation of 32Pi into myosin light chain 2. 2. Exposure of rat papillary muscle to endothelin caused an increase in isometric twitch force but did not alter the twitch-time parameters. 3. Endothelin did not significantly change the maximum contracture tension but did cause an increase in contracture tension at submaximal levels of activation, without changes in the tension-to-stiffness ratio and kinetics of attached cross-bridges. Kinetics of attached cross-bridges were deduced during steady contracture from complex-stiffness values, and in particular from the frequency at which muscle stiffness assumes a minimum value, fmin. Endothelin did not alter fmin. 4. Endothelin caused an increase in the level of incorporation of 32Pi into myosin light chain 2 without a concurrent change in the level of incorporation of 32Pi into troponin I. 5. We conclude that the inotropic action of endothelin is not due to an increase in the kinetics of attached cross-bridges, nor due to a change in the force per unit cross-bridge, but may result from an increased divalent cation sensitivity caused by elevated myosin light chain 2 phosphorylation, resembling post-tetanic potentiation in fast skeletal muscle fibres.
Rossmanith
G H
GH
Biomedical Systems Research Group, School of Mathematics, Physics, Computing and Electronics, Macquarie University-Sydney, NSW, Australia. gunther@mpce.mq.edu.au
Hoh
J F
JF
Turnbull
L
L
Ludowyke
R I
RI
D000818:Animals; D001464:Barium / Q000494:pharmacology; D024722:Cardiac Myosins; D002316:Cardiotonic Agents / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D016232:Endothelins / Q000494:pharmacology*; D007537:Isometric Contraction / Q000187:drug effects; D007700:Kinetics; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D018994:Myosin Light Chains / Q000378:metabolism*; D010210:Papillary Muscles / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010748:Phosphopeptides / Q000032:analysis; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019210:Troponin I / Q000378:metabolism
D002316:Cardiotonic Agents; D016232:Endothelins; D018994:Myosin Light Chains; D010748:Phosphopeptides; D010761:Phosphorus Radioisotopes; D019210:Troponin I; C107184:myosin light chain 2; D001464:Barium; D024722:Cardiac Myosins