TY - JOUR T1 - Activation of ATP-sensitive outward K+ current by nicorandil (2-nicotinamidoethyl nitrate) in isolated ventricular myocytes. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 278 LP - 285 VL - 250 IS - 1 AU - M Hiraoka AU - Z Fan Y1 - 1989/07/01 UR - http://jpet.aspetjournals.org/content/250/1/278.abstract N2 - The vasodilatory agent, nicorandil (2-nicotinamidoethyl nitrate) activates an outward K+ current in cardiac and vascular smooth muscle. This current was studied with the patch clamp technique using isolated guinea pig and rabbit ventricular myocytes. Nicorandil (10(-5) and 10(-4) M) shortened the action potential duration without any significant change in the resting membrane potential. Under voltage clamp, nicorandil increased the time-independent outward current at potentials positive to -80 mV, and decreased the inward current at potentials negative to -90 mV. The drug did not affect Ca++ current activated upon depolarization from the holding potential of -30 mV, or did it influence delayed outward K+ current on repolarization. In rabbit myocytes, nicorandil did not increase the Ca++-sensitive and -insensitive transient outward K+ currents. When the ATP concentration of the pipette solution was reduced from 5 to 2 to 3 mM, nicorandil produced a large increase in outward current, which decreased slightly with time. The increased outward current was antagonized by raising the intracellular ATP concentration. Nicorandil increased the probability of opening of the ATP-sensitive single channel current without affecting its unitary amplitude. These results indicate that nicorandil activates the ATP-sensitive K+ current, which is responsible for shortening of the action potential duration. ER -