JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Jiang, M. T. Articles by Bosnjak, Z. J. Search for Related Content PubMed PubMed Citation Articles by Jiang, M. T. Articles by Bosnjak, Z. J. Related Collections Mechanisms Cardiovascular Pharmacology

---

CARDIOVASCULAR ANESTHESIOLOGY

Isoflurane Activates Human Cardiac Mitochondrial Adenosine Triphosphate-Sensitive K⁺ Channels Reconstituted in Lipid Bilayers

Ming T. Jiang, MB, PhD^*, Yuri Nakae, MD, PhD^*, Marko Ljubkovic, MD, Wai-Meng Kwok, PhD^*, David F. Stowe, MD, PhD^*, and Zeljko J. Bosnjak, PhD^*

From the Departments of *Anesthesiology, Physiology, Pharmacology, and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin.

Address correspondence and reprint requests to Ming Tao Jiang, MB, PhD, Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226. Address e-mail to mtjiang{at}mcw.edu.

Abstract

BACKGROUND: Activation of the mitochondrial adenosine triphosphate (ATP)-sensitive K⁺ channel (mitoK_ATP) has been proposed as a critical step in myocardial protection by isoflurane-induced preconditioning in humans and animals. Recent evidence suggests that reactive oxygen species (ROS) may mediate isoflurane-mediated myocardial protection. In this study, we examined the direct effect of isoflurane and ROS on human cardiac mitoK_ATP channels reconstituted into the lipid bilayers.

METHODS: Inner mitochondrial membranes were isolated from explanted human left ventricles not suitable for heart transplantation and fused into lipid bilayers in symmetrical potassium glutamate solution (150 mM). ATP-sensitive K⁺ currents were recorded before and after exposure to isoflurane and H₂O₂ under voltage clamp.

RESULTS: The human mitoK_ATP was identified by its sensitivity to inhibition by ATP and 5-hydroxydecanoate. Addition of isoflurane (0.8 mM) increased the open probability of the mitoK_ATP channels, either in the presence or absence of ATP inhibition (0.5 mM). The isoflurane-mediated increase in K⁺ currents was completely inhibited by 5-hydroxydecanoate. Similarly, H₂O₂ (200 µM) was able to activate the mitoK_ATP previously inhibited by ATP.

CONCLUSIONS: These data confirm that isoflurane, as well as ROS, directly activates reconstituted human cardiac mitoK_ATP channel in vitro, without apparent involvement of cytosolic protein kinases, as commonly proposed. Activation of the mitoK_ATP channel may contribute to the myocardial protective effect of isoflurane in the human heart.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999