The Age‐dependence of atrial arrhythmogenicity in Scn5a+/−murine hearts reflects alterations in action potential propagation and recovery

Summary In the present study, we investigated the effect of age on atrial electrophysiological properties in Scn5a +/− hearts used to model corresponding increases in atrial arrhythmic tendency in human B rugada syndrome. Atrial action potential initiation, propagation and recovery were compared in young (3 month old) and aged (12 month old), wild‐type ( WT ) and Scn5a +/− hearts. Multielectrode array recordings assessed the spatial propagation of intrinsic electrical activity in superfused atrial preparations, whereas bipolar electrogram recordings measured basic cycle lengths ( BCL ) in L angendorff preparations. The duration of electrogram activity ( EGD ) during regular and extrasystolic stimulation with programmed electrical stimulation provided EGD ratios and atrial effective refractory periods ( AERP ). Monophasic recordings measured action potential durations ( APD ). Systematic statistical explorations for independent and interacting effects of age and the Scn5a +/− condition demonstrated that both young and aged Scn5a +/− mice exhibited slowed propagation of atrial excitation relative to corresponding WT mice, with the greatest effects in aged Scn5a +/− mice, which additionally exhibited increased intrinsic BCL . Young Scn5a +/− mice exhibited greater EGD and EGD ratios, as well as APD / AERP ratios, suggesting increased arrhythmic tendency compared with WT mice. Aged Scn5a +/− mice exhibited normal EGD , EGD ratios and APD compared to aged WT and young Scn5a +/− , and increased AERP and smaller APD/AERP ratios compared with young Scn5a +/− . These electrophysiological findings indicate increased atrial arrhythmogenicity with maximal effects on both conduction and repolarization characteristics in young compared with aged Scn5a +/− mice.