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.
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.
Authors: Karin E J Rödström; Aytuğ K Kiper; Wei Zhang; Susanne Rinné; Ashley C W Pike; Matthias Goldstein; Linus J Conrad; Martina Delbeck; Michael G Hahn; Heinrich Meier; Magdalena Platzk; Andrew Quigley; David Speedman; Leela Shrestha; Shubhashish M M Mukhopadhyay; Nicola A Burgess-Brown; Stephen J Tucker; Thomas Müller; Niels Decher; Elisabeth P Carpenter Journal: Nature Date: 2020-04-29 Impact factor: 49.962
Authors: Sam Chai; Xiaoping Wan; Angelina Ramirez-Navarro; Paul J Tesar; Elizabeth S Kaufman; Eckhard Ficker; Alfred L George; Isabelle Deschênes Journal: J Clin Invest Date: 2018-02-12 Impact factor: 14.808
Authors: Mark A Skarsfeldt; Thomas A Jepps; Sofia H Bomholtz; Lea Abildgaard; Ulrik S Sørensen; Emilie Gregers; Jesper H Svendsen; Jonas G Diness; Morten Grunnet; Nicole Schmitt; Søren-Peter Olesen; Bo H Bentzen Journal: Pflugers Arch Date: 2016-01-05 Impact factor: 3.657
Authors: Erin Harleton; Alessandra Besana; George M Comas; Peter Danilo; Tove S Rosen; Michael Argenziano; Michael R Rosen; Richard B Robinson; Steven J Feinmark Journal: J Biol Chem Date: 2012-12-10 Impact factor: 5.157