Knock-out of the potassium channel TASK-1 leads to a prolonged QT interval and a disturbed QRS complex

Cell Physiol Biochem. 2011;28(1):77-86. doi: 10.1159/000331715. Epub 2011 Aug 16.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Anesthetics, Inhalation / pharmacology
  • Animals
  • Electrophysiological Phenomena / physiology
  • Heart Rate / drug effects
  • Hemodynamics / physiology
  • Isoflurane / pharmacology
  • Long QT Syndrome / etiology*
  • Methoxamine / pharmacology
  • Mice
  • Mice, Knockout
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / physiology
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism*
  • Potassium Channels, Tandem Pore Domain / deficiency
  • Potassium Channels, Tandem Pore Domain / genetics*
  • Potassium Channels, Tandem Pore Domain / metabolism*
  • Sulfonamides / pharmacology*
  • ortho-Aminobenzoates / pharmacology*

Substances

  • 2-(butane-1-sulfonylamino)-N-(1-(6-methoxypyridin-3-yl)propyl)benzamide
  • Anesthetics, Inhalation
  • Nerve Tissue Proteins
  • Potassium Channels, Tandem Pore Domain
  • Sulfonamides
  • ortho-Aminobenzoates
  • potassium channel subfamily K member 3
  • Isoflurane
  • Methoxamine