Kinetic effects of myosin regulatory light chain phosphorylation on skeletal muscle contraction.
Kinetic analysis of contracting fast and slow rabbit muscle fibers in the presence of the tension inhibitor 2,3-butanedione monoxime suggests that regulatory light chain (RLC) phosphorylation up-regulates the flux of weakly attached cross-bridges entering the contractile cycle by increasing the actin-catalyzed release of phosphate from myosin. This step appears to be separate from earlier Ca(2+) regulated steps. Small step-stretches of single skinned fibers were used to study the effect of phosphorylation on fiber mechanics. Subdivision of the resultant tension transients into the Huxley-Simmons phases 1, 2(fast), 2(slow), 3, and 4 reveals that phosphorylation reduces the normalized amplitude of the delayed rise in tension (stretch activation response) by decreasing the amplitudes of phase 3 and, to a lesser extent, phase 2(slow). In slow fibers, the RLC P1 isoform phosphorylates at least 4-fold faster than the P2 isoform, complicating the role of RLC phosphorylation in heart and slow muscle. We discuss the functional relevance of the regulation of stretch activation by RLC phosphorylation for cardiac and other oscillating muscles and speculate how the interaction of the two heads of myosin could account for the inverse effect of Ca(2+) levels on isometric tension and rate of force redevelopment (k(TR)).
Davis
Julien S
JS
Molecular Physiology Section, Laboratory of Molecular Cardiology, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1760, USA. davisjs@nhlbi.nih.gov
Satorius
Colleen L
CL
Epstein
Neal D
ND
D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D002118:Calcium / Q000378:metabolism; D003001:Cloning, Molecular; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000378:metabolism*; D018994:Myosin Light Chains / Q000737:chemistry*; D010766:Phosphorylation; D020033:Protein Isoforms; D011817:Rabbits; D013997:Time Factors; D015854:Up-Regulation
D018994:Myosin Light Chains; D020033:Protein Isoforms; D002118:Calcium