Effects of ketamine on nicorandil induced ATP-sensitive potassium channel activity in cell line derived from rat aortic smooth muscle.
OBJECTIVE
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 (IC(50)=34±1 µM, n=14), but S-(+)-ketamine was less potent than ketamine racemate in blocking nicorandil induced K(ATP) channel activities (IC(50)=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.
Kawano
Takashi
T
Department of Anesthesiology, Institute of Health Biosciences, the University of Tokushima Graduate School, Kuramoto, Tokushima, Japan.
Tanaka
Katsuya
K
Yinhua
Eguchi
Satoru
S
Kawano
Hiroaki
H
Takahashi
Akira
A
Nakaya
Yutaka
Y
Oshita
Shuzo
S
D000244:Adenosine Diphosphate / Q000378:metabolism; D000778:Anesthetics, Dissociative / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D055724:Electrophysiological Phenomena; D005905:Glyburide / Q000494:pharmacology; D054086:KATP Channels / Q000187:drug effects* / Q000378:metabolism*; D007649:Ketamine / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism*; D020108:Nicorandil / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D013237:Stereoisomerism
D000778:Anesthetics, Dissociative; D054086:KATP Channels; D020108:Nicorandil; D000244:Adenosine Diphosphate; D007649:Ketamine; D005905:Glyburide