Investigations on glycerinated cardiac muscle fibres in relation to the problem of regulation of cardiac contractility--effects of Ca++ and c-AMP.

Alterations in myocardial contractile force and maximum unloaded shortening velocity (Vmax) occurring in the course of isometric twitch contraction and with changes in inotropism are assumed to be mediated by changes in intracellular Ca++ and/or c-AMP concentration. In the present study, the influences of Ca++ and cyclic AMP upon the contractility of briefly glycerinated myocardial preparations are described. It is shown that Ca2++ ions affect tension and Vmax, as measured by rectangular releases in length, in different concentration ranges. This suggests that, besides the number of attached crossbridges regulated by Ca++ binding to troponin C, a Ca++-dependent phosphorylation of the P-light chain of myocardial myosin may be involved in the regulation of Vmax. Cyclic AMP, on the other hand, induces phosphorylation of troponin I, thereby reducing the sensitivity of tension to Ca++. It is concluded that the positive inotropic effect of catecholamines may be mediated by the described actions of intracellular Ca++ and c-AMP upon the contractile structures where c-AMP-dependent troponin phosphorylation could account for the acceleration of relaxation.