Genetic Ablation of TASK-1 (Tandem of P Domains in a Weak Inward Rectifying K ⁺ Channel–Related Acid-Sensitive K ⁺ Channel-1) (K _2P 3.1) K ⁺ Channels Suppresses Atrial Fibrillation and Prevents Electrical Remodeling

Abstract

AF was associated with increased TASK-1 transcript, protein and ion current levels leading to shortened action potential duration in atrial cardiomyocytes compared to sinus rhythm controls, similar to previous findings in humans. Anti-TASK-1 adeno-associated viral application significantly reduced AF burden in comparison to untreated AF pigs. Antiarrhythmic effects of anti-TASK-1-siRNA were associated with reduction of TASK-1 currents and prolongation of action potential durations in atrial cardiomyocytes to sinus rhythm values. Conclusions Adeno-associated viral-based anti-TASK-1 gene therapy suppressed AF and corrected cellular electrophysiological remodeling in a porcine model of AF. Suppression of AF through selective reduction of TASK-1 currents represents a new option for antiarrhythmic therapy.