Localization of contractile-dependent Ca: comparison of Mn and verapamil in cardiac and skeletal muslce

The effects of two excitation-contraction uncoupling agents, manganese (Mn) and verapamil, are compared in heart and fast-twitch skeletal muscle. Particular attention is given to the effect of the agents on the first contraction following a period of quiescence when the agents are administered during the quiescent period. Mn significantly diminishes dP/dt of the first beat in heart muscle, whereas verapamil has no significant effect. Neither Mn nor verapamil has a significant effect on the first postquiescent contraction in skeletal muscle, though verapamil produces a diminution of dP/dt in subsequent contractions in both tissues. A comparison of the effect of the agents on 45Ca exchange in heart cells in tissue culture indicates that Mn induces a rapid displacement of a rapidly exchangeable component of heart-cell calcium with subsequent inhibiton of influx. Verapamil, by contrast, produces no rapid displacement but only an inhibiton of influx. The functional and Ca-exchange effect of the two agents are compatible with a model which places most of the contractile-dependent Ca at the cellular surface in heart muscle and at deeper, intracellular sites in fast-twitch skeletal muscle.