Osmotic compression of skinned cardiac and skeletal muscle bundles: effects on force generation, Ca2+ sensitivity and Ca2+ binding.
Length-dependence of myofilament Ca2+ sensitivity is now considered to be an important component of the steep relationship between active force and sarcomere length along the ascending limb of the cardiac force-length curve. Studies with skinned cardiac muscle preparations have demonstrated that Ca(2+)-troponin C affinity is significantly increased as sarcomere length is increased over the range 1.7-2.3 microns. Increase in sarcomere length is accompanied by a reduction in interfilament spacing. In skinned fiber preparations from both cardiac and skeletal muscle osmotic compression of the filament lattice enhances myofilament Ca2+ sensitivity. This study was undertaken to evaluate the hypothesis that a change in filament separation may contribute to the length-dependent activation seen in cardiac muscle. Moderate reduction in interfilament spacing caused by exposure to Dextran T-500 (5-10%) produced an increase in force generation in both maximally activated and partially activated preparations of skinned bovine ventricular muscle. With fiber bundles of mean sarcomere length 1.7 microns the addition of 5% Dextran T-500 produced an increase in Ca2+ sensitivity of about 0.25 pCa units and a significant increase in Ca2+ binding in the pCa range (6.0-5.0) in which the single regulatory site of cardiac troponin C is titrated. This concentration of Dextran T-500 produced a reduction in fiber width equivalent to that produced by stretching fibers from sarcomere length 1.7 microns to sarcomere length 2.3 microns Osmotic compression of skinned rabbit psoas muscle fibers also enhanced Ca2+ sensitivity but there was no significant change in Ca(2+)-troponin C affinity. These data suggest that 1) an important component of length-dependent Ca2+ sensitivity in both cardiac and skeletal muscle is the change in interfilament spacing, and 2) in cardiac muscle a reduction in spacing, like increase in length, leads to a specific increase in Ca(2+)-troponin C affinity. Thus both filament overlap and filament separation contribute to the length dependence of Ca2+ sensitivity and Ca2+ binding in cardiac muscle.
Wang
Y P
YP
Department of Cell Biology and Physiology, University of Pittsburgh, School of Medicine, PA 15261, USA.
Fuchs
F
F
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology*; D002417:Cattle; D003911:Dextrans; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000502:physiology; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D009997:Osmotic Pressure; D016658:Psoas Muscles / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D011817:Rabbits; D012518:Sarcomeres / Q000502:physiology / Q000648:ultrastructure; D014336:Troponin / Q000378:metabolism; D019209:Troponin C
D003911:Dextrans; D014336:Troponin; D019209:Troponin C; D002118:Calcium