TASK-1 channels may modulate action potential duration of human atrial cardiomyocytes

Cell Physiol Biochem. 2011;28(4):613-24. doi: 10.1159/000335757. Epub 2011 Dec 14.

Abstract

Background/aims: Atrial fibrillation is the most common arrhythmia in the elderly, and potassium channels with atrium-specific expression have been discussed as targets to treat atrial fibrillation. Our aim was to characterize TASK-1 channels in human heart and to functionally describe the role of the atrial whole cell current I(TASK-1).

Methods and results: Using quantitative PCR, we show that TASK-1 is predominantly expressed in the atria, auricles and atrio-ventricular node of the human heart. Single channel recordings show the functional expression of TASK-1 in right human auricles. In addition, we describe for the first time the whole cell current carried by TASK-1 channels (I(TASK-1)) in human atrial tissue. We show that I(TASK-1) contributes to the sustained outward current I(Ksus) and that I(TASK-1) is a major component of the background conductance in human atrial cardiomyocytes. Using patch clamp recordings and mathematical modeling of action potentials, we demonstrate that modulation of I(TASK-1) can alter human atrial action potential duration.

Conclusion: Due to the lack of ventricular expression and the ability to alter human atrial action potential duration, TASK-1 might be a drug target for the treatment of atrial fibrillation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology*
  • Aged
  • Animals
  • Atrial Fibrillation / metabolism
  • Atrial Fibrillation / pathology
  • Cells, Cultured
  • Electrocardiography
  • Female
  • Heart Atria / metabolism
  • Humans
  • Male
  • Middle Aged
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / physiology*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Oocytes / metabolism
  • Patch-Clamp Techniques
  • Potassium Channels, Tandem Pore Domain / genetics
  • Potassium Channels, Tandem Pore Domain / metabolism*
  • Xenopus

Substances

  • Nerve Tissue Proteins
  • Potassium Channels, Tandem Pore Domain
  • potassium channel subfamily K member 3