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Long-chain acylcarnitines regulate the hERG channel

Fabio Ferro1, Aude Ouillé, Truong-An Tran

  • 1INSERM U921, Université François-Rabelais, Tours, France.

Plos One
|August 1, 2012
PubMed

Insights

Long-chain acyl-carnitines (LCACs) affect cardiac ion channels, potentially explaining arrhythmias in conditions like ischemia. LCACs regulate hERG channel activity, influencing action potential duration and contributing to cardiac arrhythmias.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Cardiology
  • Electrophysiology

Background:

  • Carnitine levels fluctuate in pathological states, linked to cardiac arrhythmias and sudden cardiac death.
  • Acyl-carnitines (acyl-CARs), not carnitine itself, are implicated in ischemia-induced arrhythmias via ion channel modulation.

Purpose of the Study:

  • Investigate the effects of acyl-carnitines on key cardiac ion channels: hERG (IKr), K(IR)2.1 (IK1), and K(v)7.1/minK (IKs).
  • Determine the role of acyl-CARs in modulating ionic currents responsible for cardiac electrical activity.

Main Methods:

  • Utilized patch clamp electrophysiology on HEK293 cells expressing hERG, K(IR)2.1, or Kv7.1/minK channels.
  • Applied various concentrations of free carnitine and medium-chain/long-chain acyl-CARs intracellularly and extracellularly.
  • Included free fatty acids in hERG channel studies.

Main Results:

  • Extracellular long-chain acyl-CARs (LCACs) increased I(hERG) current amplitude and accelerated deactivation kinetics in a dose-dependent manner.
  • No significant effects were observed on K(IR)2.1 or Kv7.1/minK channels.
  • Computer simulations indicated that these changes in I(hERG) affect action potential profiles.

Conclusions:

  • Extracellular LCACs tonically regulate hERG channel amplitude and kinetics under physiological conditions.
  • This modulation by LCACs may contribute to altered action potential duration preceding cardiac arrhythmias.
  • Findings are relevant to understanding arrhythmias in ischemia, diabetes, and primary systemic carnitine deficiency.
Abstract

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