title: Isoflurane activates rat mitochondrial ATP-sensitive K+ channels reconstituted in lipid bilayers.
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.
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Nakae
authors.forename: Wai-Meng
authors.initials: WM
authors.lastname: Kwok
authors.forename: Zeljko J
authors.initials: ZJ
authors.lastname: Bosnjak
authors.forename: Ming Tao
authors.initials: MT
authors.lastname: Jiang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000494:pharmacology*; D008051:Lipid Bilayers / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats
chemical_list: D018685:Anesthetics, Inhalation; D008051:Lipid Bilayers; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D007530:Isoflurane