Investigating the TASK1 potassium channel in equine atrial myocardium as a potential treatment target for atrial fibrillation
Lize‐Maria Verhaeghe, Natasa Jávorszky, Manuel Kraft, Felix Wiedmann, Frederike Marie Weitkamp, Annelies Decloedt, Glenn Van Steenkiste, Gunther van Loon, Constanze SchmidtBackground 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
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.