Investigating the TASK1 potassium channel in equine atrial myocardium as a potential treatment target for atrial fibrillation

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is the most common clinically relevant arrhythmia in horses, with limited pharmacological treatment options in both veterinary and human medicine. TASK1 potassium channels represent a promising atrial-selective antiarrhythmic target, but their relevance in horses has not been established. To characterize equine TASK1 (eqTASK1) channels regarding structural conservation, electrophysiological function, pharmacological sensitivity, cardiac expression pattern and in vivo electrophysiological effects of TASK1 inhibition. EXPERIMENTAL APPROACH: Sixteen horses killed for non-cardiovascular reasons, of which 10 horses used for tissue harvesting and six horses for in vivo testing. Functional and pharmacological properties of eq TASK1 and human (hTASK1) channels were assessed in Xenopus laevis oocytes using two-electrode voltage clamp recordings. Cardiac expression of eqTASK1 was analysed by qRT-PCR and immunoblotting, while in vivo electrophysiological studies were performed in anaesthetized horses before and after intravenous ketodoxapram administration. KEY RESULTS: EqTASK1 and h TASK1 channels demonstrated high structural conservation, comparable potassium-selective background currents and preserved pharmacological sensitivity with species-dependent differences in potency. EqTASK1 expression was strongly enriched in atrial and nodal tissue, whereas ventricular expression was minimal. In vivo administration of ketodoxapram significantly prolonged atrial effective refractory periods from 275 ± 54 to 418 ± 94 ms without significant changes in heart rate or atrioventricular conduction parameters. CONCLUSION AND IMPLICATIONS: EqTASK1 channels are highly conserved with human orthologs and display pronounced atrial-predominant cardiac expression. In vivo TASK1 inhibition prolongs atrial refractoriness in horses, supporting TASK1 as a translational atrial-selective antiarrhythmic target in both human and veterinary medicine.