ACTIONS OF FLUNARIZINE, A CA++ ANTAGONIST, ON IONIC CURRENTS IN FRAGMENTED SMOOTH-MUSCLE CELLS OF THE RABBIT SMALL-INTESTINE

  • 1 March 1987
    • journal article
    • research article
    • Vol. 240  (3) , 978-983
Abstract
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 .mu.M). 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 .mu.M slowly inhibited the peak amplitude of inward current, in a voltage- and use-dependent manner. Intracellular perfusion of flunarizine, up to 100 .mu.M, 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 .mu.M) and accelerated inactivations of this current. When the command pulses (300 msec; stepped up to +2- mV from -60 mV) were applied repetitively every 20 sec, amplitudes of the K+ outward current were not affected. However, flunarizine, above 1 .mu.M, reduced the peak amplitude of the K+ 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.