Omega-3 polyunsaturated fatty acids inhibit transient outward and ultra-rapid delayed rectifier K+currents and Na+current in human atrial myocytes

Cardiovasc Res. 2009 Feb 1;81(2):286-93. doi: 10.1093/cvr/cvn322. Epub 2008 Nov 24.

Abstract

Aims: The omega-3 (n-3) polyunsaturated fatty acids (omega-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil were recently reported to have an anti-atrial fibrillation effect in humans; however, the ionic mechanisms of this effect are not fully understood. The present study was designed to determine the effects of EPA and DHA on transient outward and ultra-rapid delayed rectifier potassium currents (I(to) and I(Kur)) and the voltage-gated sodium current (I(Na)) in human atrial myocytes.

Methods and results: A whole-cell patch voltage clamp technique was employed to record I(to) and I(Kur), and I(Na) in human atrial myocytes. It was found that EPA and DHA inhibited I(to) in a concentration-dependent manner (IC(50): 6.2 microM for EPA; 4.1 microM for DHA) and positively shifted voltage-dependent activation of the current. In addition, I(Kur) was suppressed by 1-50 microM EPA (IC(50): 17.5 microM) and DHA (IC(50): 4.3 microM). Moreover, EPA and DHA reduced I(Na) in human atrial myocytes in a concentration-dependent manner (IC(50): 10.8 microM for EPA; 41.2 microM for DHA) and negatively shifted the potential of I(Na) availability. The I(Na) block by EPA or DHA was use-independent.

Conclusion: The present study demonstrates for the first time that EPA and DHA inhibit human atrial I(to), I(Kur), and I(Na) in a concentration-dependent manner; these effects may contribute, at least in part, to the anti-atrial fibrillation of omega-3 PUFAs in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Delayed Rectifier Potassium Channels / antagonists & inhibitors*
  • Docosahexaenoic Acids / pharmacology*
  • Eicosapentaenoic Acid / pharmacology*
  • Heart Atria / metabolism
  • Humans
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Potassium Channel Blockers / pharmacology*
  • Sodium Channel Blockers / pharmacology*

Substances

  • Delayed Rectifier Potassium Channels
  • Potassium Channel Blockers
  • Sodium Channel Blockers
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid