Calcium Requirements for Cardiac Myofibrillar Activation

Abstract

The amounts of calcium required to achieve various levels of myofibrillar activation in the dog heart were determined by measuring the dependence of myofibrillar calcium binding, myofibrillar adenosinetriphosphatase (ATPase), and isometric tension on free calcium concentration. Myofibrillar ATPase was half-maximal at 2.4 x 10 -6 M free calcium, and tension development was half-maximal at 2.0 x 10 -6 M free calcium. No simple relation between calcium binding and activation was found. For example, between 10 -8 M and 10 -6 M free calcium, an appreciable amount of calcium was bound to the myofibrils, but there was little activation of isometric tension. On the other hand, myofibrillar calcium binding was not saturated at levels of free calcium at which both tension and ATPase were maximal; therefore, it appears that only a portion of the total myofibrillar calcium binding sites control ATPase and tension. Using the information derived from the binding and activation studies together with our determination of the myofibrillar content of the dog heart, 47.5 mg myofibrillar protein/g wet heart, we calculated the calcium required to achieve various levels of myofibrillar activation in the intact ventricle. By this calculation method, development of half-maximal tension required 22.4 µmoles calcium/kg wet heart, and development of maximal isometric tension required 92.8 µmoles/kg wet heart.