Gene and Protein Expression Profile of Selected Molecular Targets Mediating Electrophysiological Function in Deficient Murine Atria.

Increases in the prevalence of obesity, insulin resistance, and metabolic syndrome has led to the increase of atrial fibrillation (AF) cases in the developed world. These AF risk factors are associated with mitochondrial dysfunction, previously modelled using peroxisome proliferator activated receptor-γ (PPARγ) coactivator-1 ()-deficient murine cardiac models. We explored gene and protein expression profiles of selected molecular targets related to electrophysiological function in murine atria. qPCR analysis surveyed genes related to Na⁺-K⁺-ATPase, K⁺ conductance, hyperpolarisation-activated cyclic nucleotide-gated (Hcn), Na⁺ channels, Ca channels, and indicators for adrenergic and cholinergic receptor modulation. Western blot analysis for molecular targets specific to conduction velocity (Na1.5 channel and gap junctions) was performed. Transcription profiles revealed downregulation of molecules related to Na⁺-K⁺-ATPase transport, Hcn-dependent pacemaker function, Na⁺ channel-dependent action potential activation and propagation, Ca current generation, calsequestrin-2 dependent Ca homeostasis, and adrenergic α dependent protection from hypertrophic change. Na1.5 channel protein expression but not gap junction expression was reduced in atria compared to . Na1.5 reduction reflects corresponding reduction in its gene expression profile. These changes, as well as the underlying alteration, suggest potential pharmacological targets directed towards either upstream PGC-1 signalling mechanisms or downstream ion channel changes.