Isoflurane‐induced cardioprotection: role of sarcolemmal KATP channels and mitochondria

Abstract

We investigated the role of sarcKATP channels and mitochondria in anesthetic-induced preconditioning (APC) using a knockout mouse model with deleted Kir6.2 subunit, the pore-forming part of sarcKATP channel (Kir6.2 C57BL/6 KO). Flavoprotein (FP) fluorescence, reactive oxygen species (ROS) production, and mitochondrial membrane potential, were monitored in isolated myocytes by laser scanning confocal microscopy during exposure to 1 MAC isoflurane. In the presence of isoflurane FP fluorescence increased to 180% and 190% of baseline in cardiomyocytes of WT and Kir6.2 KO mice, respectively. ROS increased to 118% and 124% of baseline in WT and Kir6.2 KO myocytes. Mitochondrial membrane potential decreased to 87% and 86% of baseline in WT and Kir6.2 KO. Oxidative stress induced cell death in 31% and 44% of WT and Kir6.2 KO. APC attenuated cell death to 21% and 35% in WT and Kir6.2 KO myocytes. Deletion of pore-forming subunit of sarcKATP channel did not alter characteristic mitochondrial responses to isoflurane in Kir6.2 KO cardiomyocytes. APC is preserved in the Kir6.2 KO cardiomyocytes, but their susceptibility to oxidative stress appears greater under basal conditions. Thus, sarcKATP channels are an important component of a cardioprotective pathway independent of mitochondria-mediated protection. Supported by P01GM066730 (ZJB) from the NIH, Bethesda, MD.