Activation of ATP-sensitive outward K+ current by nicorandil (2-nicotinamidoethyl nitrate) in isolated ventricular myocytes.
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.
Hiraoka
M
M
Department of Cardiovascular Diseases, Medical Research Institute, Tokyo Medical and Dental University, Japan.
Fan
Z
Z
D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology; D004553:Electric Conductivity; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology*; D016276:Ventricular Function
D015221:Potassium Channels; D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil; D003035:Cobalt; D000255:Adenosine Triphosphate; D002118:Calcium