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

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. 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 (IC50: 6.2 mu M for EPA; 4.1 mu M for DHA) and positively shifted voltage-dependent activation of the current. In addition, I-Kur was suppressed by 1-50 mu M EPA (IC50: 17.5 mu M) and DHA (IC50: 4.3 mu M). Moreover, EPA and DHA reduced I-Na in human atrial myocytes in a concentration-dependent manner (IC50: 10.8 mu M for EPA; 41.2 mu M for DHA) and negatively shifted the potential of I-Na availability. The I-Na block by EPA or DHA was use-independent. 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.