Knock-Out of the Potassium Channel TASK-1 Leads to a Prolonged QT Interval and a Disturbed QRS Complex

Background/Aims: The aim of the study was to characterize the whole cell current of the two-pore domain potassium channel TASK-1 (K2P3) in mouse ventricular cardiomyocytes (I TASK-1 ) and to analyze the cardiac phenotype of the TASK-1 -/- mice. Methods and Results: We have quantified the ventricular I TASK-1 current using the blocker A293 and TASK-1 -/- mice. Surface electrocardiogram recordings of TASK-1 -/- mice showed a prolonged QTc interval and a broadened QRS complex. The differences in electrocardiograms between wild type and TASK-1 -/- mice disappeared during sympathetic stimulation of the animals. Quantitative RT-PCR, patch clamp recordings and measurements of hemodynamic performance of TASK-1 -/- mice revealed no major compensatory changes in ion channel transcription. Action potential recordings of TASK-1 -/- mouse cardiomyocytes indicated that I TASK-1 modulates action potential duration. Our in vivo electrophysiological studies showed that isoflurane, which activates TASK-1, slowed heart rate and atrioventricular conduction of wild-type but not of TASK-1 -/- mice. Conclusion: The results of an invasive electrophysiological catheter protocol in combination with the observed QRS time prolongation in the surface electrocardiogram point towards a regulatory role of TASK-1 in the cardiac conduction system.