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

Abstract

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