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

抄録

Purpose: Nicorandil opens adenosine triphosphate-sensitive potassium (K_ATP) 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 K_ATP 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 K_ATP channels in cultured rat aortic smooth muscle cells. Furthermore, we also investigated whether intracellular MgADP could modulate ketamine inhibition. Results: Nicorandil significantly activated K_ATP channel activity, whereas this channel activity was completely blocked by glibenclamide, a specific K_ATP channel blocker. Ketamine racemate inhibited the nicorandil induced K_ATP channel activity (IC₅₀=34±1 µM, n=14), but S-(+)-ketamine was less potent than ketamine racemate in blocking nicorandil induced K_ATP 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 K_ATP channel activities. Conclusions: Our results indicate that ketamine inhibits nicorandil induced K_ATP channel activities in a dose dependent and stereoselective manner. Furthermore, increase of intracellular MgADP attenuates the inhibitory potency of ketamine racemate. J. Med. Invest. 57: 237-244, August, 2010