Actions of quinidine and apamin on after-hyperpolarization of the spike in circular smooth muscle cells of the guinea-pig ileum.

The effects of quinine and quinidine on membrane potential and action potential were investigated in circular smooth muscle of the guinea-pig ileum and the findings compared with the actions of apamin. In addition to results obtained from microelectrode experiments, the actions of quinidine and apamin on membrane currents were assessed using the single cell voltage clamp method. Quinine (above 0.2 mmol/l) and quinidine (above 0.08 mmol/l) depolarized the membrane, increased the membrane resistance and blocked generation of the after-hyperpolarization of the spike. Higher concentrations of both agents reduced the amplitude of the action potential and further depolarized the membrane. Quinidine and quinine possessed much the same action, with the former being more potent than the latter. Apamin, an inhibitor of the Ca-dependent K current, did not inhibit the after-hyperpolarization of the spike and had no effect on the membrane potential. In voltage clamp experiments, a depolarizing pulse (above -30 mV from -60 mV; 200 ms duration) elicited an inward current, followed by an outward current. With application of 2.5 mmol/l Mn instead of Ca, the outward current was subclassified into the Mn sensitive (Ca-dependent) and Mn resistant (voltage-dependent) K currents. Apamin (0.1 mumol/l) did not modify membrane currents evoked in the circular muscle cell, while, 0.1 mmol/l quinidine inhibited both the Ca- and voltage-dependent K outward currents, and Ca inward current. Our observation suggest that apamin-insensitive Ca-dependent K channels are present in the smooth muscle membrane and that they probably participate in the falling phase and after-hyperpolarization of the action potential.