Actions of flunarizine, a Ca++ antagonist, on ionic currents in fragmented smooth muscle cells of the rabbit small intestine.

Actions of flunarizine on the Ca++ inward and K+ outward currents were investigated using fragmented smooth muscle cells (smooth muscle ball) prepared from the longitudinal muscle layer of the rabbit ileum. Flunarizine dose dependently inhibited the Ca++ inward current (ID50 = 1.4 microM). The decay of the inward current consisted of two exponentials and flunarizine had no effect on these time constants. When command pulses (100 msec; stepped up to 0 mV from -60 mV) were applied every 20 sec, the peak amplitude of the inward current remained unchanged. Flunarizine above 0.3 microM slowly inhibited the peak amplitude of inward current, in a voltage- and use-dependent manner. Intracellular perfusion of flunarizine, up to 100 microM, did not modify the peak amplitude of the inward current. This Ca++ antagonist also inhibited the K+ outward current, in a dose-dependent manner (ID50 = 5.8 microM) and accelerated inactivations of this current. When the command pulses (300 msec; stepped up to +20 mV from -60 mV) were applied repetitively every 20 sec, amplitudes of the K+ outward current were not affected. However, flunarizine, above 1 microM, reduced the peak amplitude of the K+ outward current slowly. These results indicate that although flunarizine possesses the property of a Ca++ antagonist, it also inhibits the K+ outward current, in a manner different from that observed on the Ca++ inward current.