Effects of ketamine on nicorandil induced ATP-sensitive potassium channel activity in cell line derived from rat aortic smooth muscle

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Purpose : Nicorandil opens adenosine triphosphate-sensitive potassium (KATP)channels in the cardiovascular system and is being increasingly used for the treatmentof angina pectoris. In the present study, we tested whether intravenous anesthetic agentketamine affected nicorandil-induced native vascular KATP channel activation. Methods :We used excised inside-out patch clamp configurations to investigate the direct effectsof ketamine racemate and S-(+)-ketamine on the activities of KATP channels in culturedrat aortic smooth muscle cells. Furthermore, we also investigated whether intracellularMgADP could modulate ketamine inhibition. Results : Nicorandil significantly activatedKATP channel activity, whereas this channel activity was completely blocked by glibenclamide,a specific KATP channel blocker. Ketamine racemate inhibited the nicorandil inducedKATP channel activity (IC50=34 1M, n=14), but S-(+)-ketamine was less potent than ketamineracemate in blocking nicorandil induced KATP channel activities (IC50=226 7M,n=10). Application of MgADP to the intracellular side of the channel was able to decreasethe inhibitory potency of ketamine racemate on nicorandil induced KATP channel activities.Conclusions : Our results indicate that ketamine inhibits nicorandil induced KATP channelactivities in a dose dependent and stereoselective manner. Furthermore, increase ofintracellularMgADP attenuates the inhibitory potency of ketamine racemate.