Mechanisms of actions of organic and inorganic Ca antagonists.

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The effects of organic and inorganic Ca antagonists were investigated by means of the patch and whole cell voltage clamp techniques applied to dispersed single smooth muscle cells. Three different types of single channel currets ( <K_L> , <K_M> and <K_S> ) were recorded from the rabbit portal vein. All were K-selective currents, and <K_L> and <K_S> were depended on <Ca_i> . <K_M> was activated by <Ca_o> and showed no voltage-dependency at 2.8 mM <Ca_o> . Such behavior of the <K_M> channel has not yet heretofore been evidenced and possibly contributes the resting membrane currents. While organic Ca antagonists such as nifedipine or nisoldipine had no actions on <K_L> , Mg and Ba did inhibit <K_L> . Mg reduced the amplitude of the "apparent" single channel current and Ba reduced frequency of the channel opening, without affecting the amplitude. These results suggest that the membrane depolarization induced by a high concentration of the organic Ca antagonists observed with the microelectrode experiments, was not due to an inhibition of <K_L> .Effects of organic Ca antagonists on the macroscopic membrane currents were also investigated. The inward current was evoked by the depolarizing pulse and nicaldipine, diltiazem and verapamil inhibited the inward current; sequence being nicardipine verapamil diltiazem. Verapamil inhibited the inward current, in a frequency, use-dependent manner. In contrast, nicardipine inhibited the current, in a voltage-dependent manner. Thus, resting membrane potentials of the smooth muscle cells were closely linked to inhibition of the inward current seen in the presence of the Ca antagonists. In smooth muscle cells of the rabbit ileal longitudinal muscle and portal vein, these Ca antagonists had no effect when applied to the intracellular side of the membrane, therefore, the outer surface of the membrane is probably involved in such effects.