Abstract 11788: Mitochondrial Connexin43 and Mitochondrial KATP Channels Affect the Occurrence of Arrhythmias

IntroductionConnexin43 (Cx43) forms gap junction channels in the heart and is also present in the inner mitochondrial membrane (mCx43). We have previously reported that carbenoxolone, a blocker of Cx43, increases the occurrence of triggered arrhythmias under the modulation of mitochondrial KATP channels (mKATP). Thus, using cardiac-specific Cx43-deficient (Cx43) mice, we examined how Cx43 and mKATP affect the occurrence of triggered arrhythmias in ventricular muscle.MethodsOffspring of Cx43 mice and α-myosin heavy chain (Myh6)-cre mice, Cx43/ Myh6-cre mice (Cx43 mice) and their littermates (Cx43 mice), were used for experiments. Trabeculae were obtained from their right ventricles. Force and intracellular Ca (Cai) were measured (22°C). To assess arrhythmogenesis, the minimal extracellular Ca concentration (Caomin), at which arrhythmias were induced by electrical stimulation (0.3-s stimulus intervals for 30 s, 100 nM isoproterenol), was determined. Using isolated single mouse ventricular myocytes, Ca spark rate was measured with fluo-4, mitochondrial membrane potential (ΔΨm) was estimated using tetramethylrhodamine methylester (TMRM) fluorescence, and ROS production was estimated using 2’,7’-dichlorofluorescein (DCF) fluorescence.ResultsCx43 was present in the inner mitochondrial membrane in Cx43 mice but not in Cx43 mice. The Caomin in Cx43 mice was lower than that in Cx43 mice (p