Reduced Na+ current, rather than altered K+ current, is implicated as the mechanism for slowed conduction causing atrial arrhythmogenicity in energetically deficient Pgc-1β−/− hearts.
Reduced Na+ current may drive arrhythmogenicity in Pgc-1β−/− hearts; leaves open translation to clinical AF.
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. 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. 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.
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Valli et al. (2017) studied this question.
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