Endothelin blocks ATP-sensitive K channels and depolarizes smooth muscle cells of porcine coronary artery. Circ Res

ATP-sensitive K ' channels with a conductance of 30 pS in smooth muscle cells of porcine coronary artery were found to be highly active in the intact cell-attached patch configuration when the pipette contained a physiological concentration of Ca2 ' (>10- ` M). In the inside-out configuration, these channels were activated by extracellular Ca2 ' and blocked by cytosolic ATP and glibenclamide. Endothelin applied to the pipette specifically blocked these channels in a concentration-dependent manner in the cell-attached configuration (half-maximal inhibition, 1.3 x10 ` M). A K ' channel opener, nicorandil, activated these channels even in the presence of 10-8 M endothelin. In the whole-cell current-clamp method, the cell membrane was depolarized by endothelin and then repolarized by nicorandil. The membrane depolar-ization is closely related to contraction of smooth muscle cells. These results suggest that the ATP-sensitive K ' channels are important in controlling the vascular tone of the coronary artery and that endothelin can increase vascular tone by blocking these channels. (Circulation Research 1992;70:612-616