Molecular Mechanisms Underlying Ketamine-Mediated Inhibition Of
Anesthesiology 2005; 102:93–101 © 2004 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Molecular Mechanisms Underlying Ketamine-mediated Inhibition of Sarcolemmal Adenosine Triphosphate- sensitive Potassium Channels Takashi Kawano, M.D.,* Shuzo Oshita, M.D.,† Akira Takahashi, M.D.,‡ Yasuo Tsutsumi, M.D.,* Katsuya Tanaka, M.D.,§ Yoshinobu Tomiyama, M.D., Hiroshi Kitahata, M.D.,# Yutaka Nakaya, M.D.** Background: Ketamine inhibits adenosine triphosphate-sen- sensitive channel pore.3 These channels, as metabolic sitive potassium (KATP) channels, which results in the blocking sensors, are associated with such cellular functions as of ischemic preconditioning in the heart and inhibition of va- insulin secretion, cardiac preconditioning, vasodilata- sorelaxation induced by KATP channel openers. In the current 4–7 Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/102/1/93/357819/0000542-200501000-00017.pdf by guest on 27 September 2021 study, the authors investigated the molecular mechanisms of tion, and neuroprotection. ketamine’s actions on sarcolemmal KATP channels that are re- In cardiac myocytes, intravenous general anesthetics, associated by expressed subunits, inwardly rectifying potas- such as ketamine racemate, propofol, and thiamylal, di- sium channels (Kir6.1 or Kir6.2) and sulfonylurea receptors 8–10 rectly inhibit native sarcolemmal KATP channels. Al- (SUR1, SUR2A, or SUR2B). though these observations suggest that intravenous an- Methods: The authors used inside-out patch clamp configura- tions to investigate the effects of ketamine on the activities of esthetics may impair the endogenous organ protective reassociated Kir6.0/SUR channels containing wild-type, mutant, mechanisms mediated by KATP channels, the possibility or chimeric SURs expressed in COS-7 cells.
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