title: Omega-3 polyunsaturated fatty acids inhibit transient outward and ultra-rapid delayed rectifier K+currents and Na+current in human atrial myocytes.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine and Research Centre of Heart, Brain, Hormone and Healthy Aging, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong, SAR, China. grli@hkucc.hku.hk
authors.forename: Gui-Rong
authors.initials: GR
authors.lastname: Li
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Sun
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Zhang
authors.forename: Lik-Cheung
authors.initials: LC
authors.lastname: Cheng
authors.forename: Shui-Wah
authors.initials: SW
authors.lastname: Chiu
authors.forename: Hung-Fat
authors.initials: HF
authors.lastname: Tse
authors.forename: Chu-Pak
authors.initials: CP
authors.lastname: Lau
mesh_terms: D051668:Delayed Rectifier Potassium Channels / Q000037:antagonists & inhibitors*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D006325:Heart Atria / Q000378:metabolism; D006801:Humans; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D026941:Sodium Channel Blockers / Q000494:pharmacology*
chemical_list: D051668:Delayed Rectifier Potassium Channels; D026902:Potassium Channel Blockers; D026941:Sodium Channel Blockers; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid