Abstract
Introduction: Ageing and chronic metabolic disorders are associated with mitochondrial dysfunction and cardiac pro-arrhythmic phenotypes which were recently attributed to slowed atrial and ventricular action potential (AP) conduction in peroxisome proliferator-activated receptor gamma co-activator deficient (Pgc-1 beta(-/-)) mice. Methods: We compared expression levels of voltage-gated Na channel (Na(V)1.5) and gap junction channels, Connexins 40 and 43 (Cx40 and Cx43) in the hearts of young and old, and wild-type (WT) and Pgc-beta(-/-) mice. This employed Western blotting (WB) for Na(V)1.5, Cx40 and Cx43 in atrial/ventricular tissue lysates, and immunofluorescence (IF) from Cx43 was explored in tissue sections. Results were analysed using two-way analysis of variance (ANOVA) for independent/interacting effects of age and genotype. Results: In atria, increased age and Pgc-1 beta(-/-) genotype each independently decreased both Cx40 and Cx43 expression without interacting effects. In IF experiments, both age and Pgc-1 beta deletion independently reduced Cx43 expression. In ventricles, age and genotype exerted interacting effects in WB studies of Na(V)1.5 expression. Young Pgc1 beta(-/-) then showed greater Na(V)1.5 expression than young VVT ventricles. However, neither age nor Pgc-beta(-/-) deletion affected Cx43 expression, independently or through interacting effects in both WB and IF studies. Conclusion: Similar pro-arrhythmic atrial/ventricular phenotypes arise in aged/Pgc-beta(-/-) from differing contributions of altered protein expression and functional effects that may arise from multiple acute mechanisms.