Selective modulation of the ATP-sensitive K+ channel by nicorandil in guinea-pig cardiac cell membrane.
Effects of a vasodilator, nicorandil (2-nicotinamidoethyl nitrate) on four kinds for cardiac K+ channels were investigated in guinea pig ventricular and atrial cells using inside-out patch recording combined with "oil-gate" concentration jump method. Nicorandil of 300 mumols/l failed to affect the inward-rectifier K+ channel and the Na(+)-activated K+ channel. The open probability of the muscarinic K+ channel, when activated by the application of GTP, was not changed by the drug. Nicorandil selectively increased the open probability of the ATP-sensitive K+ channel that was partly suppressed by intracellular ATP. The median effective concentration (EC50) of nicorandil was 74 mumols/l and Hill coefficient was 1.32 in the concentration-open probability relationship. The closing rate of the K+ channel by ATP was markedly delayed by the drug, whereas the open rate on removal of ATP was scarcely affected. Nicorandil had only little effect on this channel after run-down. It was concluded that nicorandil selectively activates the ATP-sensitive K+ channel mainly by modulating the ATP-dependent gate.
Takano
M
M
Department of Physiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Noma
A
A
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D009206:Myocardium / Q000166:cytology; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
D015221:Potassium Channels; D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil; D000255:Adenosine Triphosphate