Bound calcium and force development in skinned cardiac muscle bundles: effect of sarcomere length.
There is evidence that the steep ascending limb of the force-length curve in cardiac muscle (Frank-Starling relation) is based on a length-dependence of myofilament Ca2+ sensitivity. Previous work from this laboratory has indicated that in the sarcomere length range corresponding to the ascending limb of the cardiac force length curve (1.7 to 2.3 microns) the Ca2+-troponin C affinity is length-dependent. In this study Ca2+ binding to chemically skinned bovine cardiac muscle bundles was measured during ATP-induced force generation with fiber bundles having sarcomere lengths of 2.2 to 2.4 microns and 1.6 to 1.8 microns. A double isotope technique was used to make concurrent determinations of the force-pCa and bound Ca2+-pCa relationships. At the longer sarcomere lengths the fibers bound, at saturation, an amount of Ca2+ equivalent to approximately 3 mol Ca2+/mol troponin C. Force development appeared to be coupled to titration of the single, low-affinity Ca2+-specific site. In the pCa range 7.0 to 6.0 sarcomere length had no effect on Ca2+ binding. In the pCa range 6.0 to 5.0, in which force increased steeply, there was, in addition to a decreased relative force, a significant reduction in bound Ca2+ at the shorter sarcomere length. Thus sarcomere length appears to influence the Ca2+ binding properties of the regulatory site on troponin C. These data provide direct evidence that length-dependent modulation of Ca2+-troponin C affinity may make a major contribution to the force-length relationship in cardiac muscle.
Hofmann
P A
PA
Department of Physiology, University of Pittsburgh School of Medicine, PA 15261.
Fuchs
F
F
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D005947:Glucose / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D009200:Myocardial Contraction; D009210:Myofibrils / Q000502:physiology*; D012518:Sarcomeres / Q000502:physiology*; D016276:Ventricular Function
D005947:Glucose; D002118:Calcium