Effects of organic Ca-antagonists on the Na current in rabbit dipersed ventricular cells.

Abstract Effects of organic Ca-antagonists on the Ma current were investigated in rabbit dispersed ventricular cells by the suction pipette method. Drugs used were diltiazem (DL), verapamil (VR), nifedipine (NF) and nicardipine (NC). The Na current remained unaffected in the presence of MF and NC at concentrations below 0.1 μM, but VR and DL at a concentration of 0.1 μM started to reduce the maximal peak amplitude (MPA) of the Na current. Higher concentrations of the Ca-antagonists induced a decrease in the MPA of the Ma current, and the effects mere dnse-dependent. The current-voltage relationships showed that the current amplitude was reduced at all membrane potentials without any change in the potential at which the maximal inward current was induced. The effects of DL (1 μM), VR (1 μM), NF (1G μM) and NC (10 μM) on the steady state inactivation and the reactivation process of the Ma current were investigated. The Ca-antagonists shifted the midpoint of the steady-state inactivation curve in the hyperpoiarizing direction by 4 to 7 mV and made the curve slightly steeper. The half reactivation time in the control was 24 to 27 msec, but the time for half-reactivation in the presence of these agents was significantly prolonged to about 40 msec or more. The results allowed interpretation of mechanisms by which DL and VR exert antiarrhythmic actions at clinical doses.