title: Knock-out of the potassium channel TASK-1 leads to a prolonged QT interval and a disturbed QRS complex.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Institut für Physiologie, Vegetative Physiologie, Universität Marburg, Marburg, Germany. decher@staff.uni-marburg.de
authors.forename: Niels
authors.initials: N
authors.lastname: Decher
authors.forename: Konstantin
authors.initials: K
authors.lastname: Wemhöner
authors.forename: Susanne
authors.initials: S
authors.lastname: Rinné
authors.forename: Michael F
authors.initials: MF
authors.lastname: Netter
authors.forename: Marylou
authors.initials: M
authors.lastname: Zuzarte
authors.forename: Maria I
authors.initials: MI
authors.lastname: Aller
authors.forename: Susann G
authors.initials: SG
authors.lastname: Kaufmann
authors.forename: Xian Tao
authors.initials: XT
authors.lastname: Li
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
authors.forename: Jürgen
authors.initials: J
authors.lastname: Daut
authors.forename: Frank B
authors.initials: FB
authors.lastname: Sachse
authors.forename: Sebastian K G
authors.initials: SK
authors.lastname: Maier
mesh_terms: D000200:Action Potentials / Q000502:physiology; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D055724:Electrophysiological Phenomena / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000502:physiology; D007530:Isoflurane / Q000494:pharmacology; D008133:Long QT Syndrome / Q000209:etiology*; D008729:Methoxamine / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology*; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
chemical_list: C577579:2-(butane-1-sulfonylamino)-N-(1-(6-methoxypyridin-3-yl)propyl)benzamide; D018685:Anesthetics, Inhalation; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; D013449:Sulfonamides; D062367:ortho-Aminobenzoates; C420132:potassium channel subfamily K member 3; D007530:Isoflurane; D008729:Methoxamine