Functional differentiation of the transmembrane sodium and calcium channels in mammalian cardiac fibers by use of specific inhibitors.

During excitation of the mammalian ventricular myocardium two transmembrane inward currents occur: a fast Na current and a slow current carried mainly by Ca. The Ca current is strongly reduced by some organic compounds like verapamil and compound D 600 which are known to be very effective inhibitors of excitation contraction coupling. A similar decrease in the Ca conductivity of the membrane is produced by the bivalent cations, Ni, Co, and Mn. The blocking action of these organic and inorganic inhibitors is reversed by increasing the extracellular Ca concentration. The slow inward current can also be restored by Sr and Ba ions. The reduction of the slow Ca current produced by verapamil, D 600, Ni, Co, or Mn occurs selectively since the fast Na current remains practically unchanged. This demonstrates the existence of two separate membrane channels for Na and Ca which can be blocked independently. Thus it is possible to modify the contractility of the myocardial cell via the magnitude of the Ca current without disturbance of the transmembrane Na current which is intimately connected with excitability.