WAY-120,491 ACTIVATES ATP-SENSITIVE POTASSIUM CHANNELS IN RAT TAIL ARTERY

WAY 120,491 lowers blood pressure in a number of animal models. Its mechanism of action appears to be the selective opening of K+ channels in vascular smooth muscle cells. The patch clamp technique was used to determine the specific K+ channel affected by WAY 120,491 in isolated tail artery cells of the rat. In the inside-out configuration, WAY 120.491 caused a dose dependent partial reversal of the ATP-induced inactivation of channel activity. Glyburide (10 muM) almost completely inhibited the effect of WAY 120,491. WAY 120,491 had no effect on Ca-activated K+ channels inactivated by the absence of Ca2+. In the whole cell configuration, 10 muM WAY 120,491 increased outward K+ current. 10 muM glyburide completely reversed the increase in current. WAY 120,491 appears to be a relatively specific activator of ATP-sensitive K+ channels in vascular smooth muscle.