Faculty Collaboration Database

Isoflurane activates rat mitochondrial ATP-sensitive K+ channels reconstituted in lipid bilayers. Am J Physiol Heart Circ Physiol 2003 May;284(5):H1865-71

Date

02/08/2003

Pubmed ID

12573994

DOI

10.1152/ajpheart.01031.2002

Scopus ID

2-s2.0-0037405092 (requires institutional sign-in at Scopus site)   57 Citations

Abstract

Activation of mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channels is critical in myocardial protection induced by preconditioning with volatile anesthetics or brief periods of ischemia. In this study, we characterized rat mitoK(ATP) channels reconstituted in lipid bilayers and examined their direct regulation by isoflurane. Mitochondria and the inner membrane fraction were isolated from rat ventricles and fused into lipid bilayers. On the basis of their inhibition by 5-hydroxydecanoate (5-HD)/ATP or activation by diazoxide, mitoK(ATP) channels of several conductance states were observed in symmetrical (150 mM) potassium glutamate (26, 47, 66, 83, and 105 pS). Isoflurane (0.8 mM) increased the cumulative open probability from 0.09 +/- 0.02 at baseline to 0.50 +/- 0.09 (P < 0.05, n = 5), which was inhibited by 5-HD. Isoflurane caused a dose-dependent rightward shift in ATP inhibition of mitoK(ATP) channels, which increased the IC(50) for ATP from 335 +/- 4 to 940 +/- 34 microM at 0.8 mM (P < 0.05, n = 5 approximately 8). We conclude that direct activation of the mitoK(ATP) channel by isoflurane is likely to contribute to volatile anesthetic-induced myocardial preconditioning.

Author List

Nakae Y, Kwok WM, Bosnjak ZJ, Jiang MT

Author

Wai-Meng Kwok PhD Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphate
Anesthetics, Inhalation
Animals
Ischemic Preconditioning, Myocardial
Isoflurane
Lipid Bilayers
Mitochondria
Myocardium
Potassium Channels
Rats