Activation of mitochondrial ATP-sensitive K+ (mitoKATP) channels is critical in myocardial protection induced by preconditioning with volatile anesthetics or brief periods of ischemia. In this study, we characterized rat mitoKATP 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, mitoKATP 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 mitoKATP channels, which increased the IC50 for ATP from 335 ± 4 to 940 ± 34 μM at 0.8 mM ( P < 0.05, n = 5∼8). We conclude that direct activation of the mitoKATP channel by isoflurane is likely to contribute to volatile anesthetic-induced myocardial preconditioning.
Myocardial Preconditioning With Volatile Anesthetics: Goodbye to All That?
