Evidence for a force-dependent component of calcium binding to cardiac troponin C.
The duration of activation in cardiac muscle is a function of the load. On the basis of studies of Ca2+ transients in muscles subjected to quick release, it has been suggested that force or shortening-mediated changes in Ca2+-troponin C affinity may provide a mechanism for a contraction-activation feedback. This study was designed to test the hypothesis that the formation of force-generating complexes between actin and myosin enhances the affinity of cardiac troponin C for Ca2+. This was done by first establishing the normal relationship between Ca2+ binding and force development in chemically skinned bovine ventricular muscle bundles and then comparing the Ca2+-saturation curves obtained with relaxed and contracting muscle bundles. A double isotope technique was used to measure Ca2+ binding during ATP-induced force generation and during relaxation maintained by the phosphate analogue vanadate. The results showed that the generation of force was associated with an enhanced binding of Ca2+ to the Ca2+-specific regulatory site of cardiac troponin C. These data provide direct evidence that feedback between force and activation in the heart may be mediated by the Ca2+-regulatory site of troponin C.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D014336:Troponin / Q000378:metabolism*; D019209:Troponin C; D014638:Vanadates / Q000494:pharmacology
D014336:Troponin; D019209:Troponin C; D014638:Vanadates; D000255:Adenosine Triphosphate; D002118:Calcium