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

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 (Ito and IKur) and the voltage-gated sodium current (INa) in human atrial myocytes. Methods and results A whole-cell patch voltage clamp technique was employed to record Ito and IKur, and INa in human atrial myocytes. It was found that EPA and DHA inhibited Ito in a concentration-dependent manner (IC50: 6.2 µM for EPA; 4.1 µM for DHA) and positively shifted voltage-dependent activation of the current. In addition, IKur was suppressed by 1–50 µM EPA (IC50: 17.5 µM) and DHA (IC50: 4.3 µM). Moreover, EPA and DHA reduced INa in human atrial myocytes in a concentration-dependent manner (IC50: 10.8 µM for EPA; 41.2 µM for DHA) and negatively shifted the potential of INa availability. The INa block by EPA or DHA was use-independent. Conclusion The present study demonstrates for the first time that EPA and DHA inhibit human atrial Ito, IKur, and INa in a concentration-dependent manner; these effects may contribute, at least in part, to the anti-atrial fibrillation of omega-3 PUFAs in humans.