Cromakalim blocks CA currents and reduces K currents in canine colonic smooth muscle cells

CROMAKALIM BLOCKS CA CURRENTS AND RRUUCES K CURRENTS IN CANINE COLONIC SMOOTH MUSCLR CELLS. J.M. Post, R. Stevens, K.M. Sanders and J.R. Hume Dept. of Physiology, Univ. of Nevada, Reno, NV 89557, USA. We have investigated the effects of the putative K channel opener, cromakalim (BRL 34915), on electrical slow wave activity in intact muscles and on voltage-dependent currents in isolated smooth muscle cells from the circular layer of the canine proximal colon. In intact muscles, cromakalim (10 30 FM) reduced the upstroke amplitude and decreased the amplitude and duration of the plateau phase of slow waves. These effects were accompanied by a hyperpolarization of the membrane potential. In isolated cells, studied under voltage clamp with the patch clamp technique, cromakalim (10 30 MM) reduced the magnitude of outward K currents elicited during depolarizing test potentials. In cells pretreated with the Ca channel antagonist, nisoldipme, cromakalim failed to reduce K current amplitude. In cells exposed to K channel antagonists and impermeant ions, depolarizing voltage clamp steps elicited inward Ca currents, which were inhibited by exposure to cromakalim (10 30 PM). We conclude that cromakalim, in addition to acting as a K channel agonist, possesses significant Ca channel antagonist properties. These properties resemble those of another putative K channel agonist, minoxidil sulfate (Circ. Res. 65: 1102, 1989). The Ca channel blocking effects of eromakalim may explain some of the actions of this agent on slow waves of intact muscles. (Supported by NIH grant DK 41315 and an AHA grant-inaid)