Cardiomyocyte ionic currents in intact young and aged murine Pgc-1β-/- atrial preparations.

Abstract Introduction Recent studies reported that energetically deficient murine Pgc-1β −/− hearts replicate age-dependent atrial arrhythmic phenotypes associated with their corresponding clinical conditions, implicating action potential (AP) conduction slowing consequent upon reduced AP upstroke rates. Materials and methods We tested a hypothesis implicating Na + current alterations as a mechanism underlying these electrophysiological phenotypes. We applied loose patch-clamp techniques to intact young and aged, WT and Pgc-1β −/− , atrial cardiomyocyte preparations preserving their in vivo extracellular and intracellular conditions. Results and discussion Depolarising steps activated typical voltage-dependent activating and inactivating inward (Na + ) currents whose amplitude increased or decreased with the amplitudes of the activating, or preceding inactivating, steps. Maximum values of peak Na + current were independently influenced by genotype but not age or interacting effects of genotype and age on two-way ANOVA. Neither genotype, nor age, whether independently or interactively, influenced voltages at half-maximal current, or steepness factors, for current activation and inactivation, or time constants for recovery from inactivation following repolarisation. In contrast, delayed outward (K + ) currents showed similar activation and rectification properties through all experimental groups. These findings directly demonstrate and implicate reduced Na + in contrast to unchanged K + current, as a mechanism for slowed conduction causing atrial arrhythmogenicity in Pgc-1β −/− hearts.