The n-3 polyunsaturated fatty acids from fish oil inhibit transient outward and ultra-rapid delayed rectifier potassium currents and voltage-gated sodium current in human atrial myocytes

Abstract

Background and Objectives: There is growing clinical evidence that the n-3 polyunsaturated fatty acids (n-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have antiarrhythmic effects (including anti-atrial fibrillation) in humans; however, their ionic mechanisms are not fully understood. The aim of the present study was to investigate the effects of n-3 PUFAs from fish oil on transient outward and ultra-rapid delayed rectifier potassium currents (Ito and IKur), and voltage-gated sodium current (INa) in human atrial myocytes. Methods: Cardiac myocytes were enzymatically isolated from human atrial specimens from patients undergoing coronary artery bypass operation. Ito, IKur, and INa were recorded using whole-cell patch configuration. Result: EPA and DHA inhibited Ito in a concentration-dependent manner (IC50: 5.1 mM for EPA; 3.8 mM mM for DHA), positively shifted voltage-dependent-activation of the current. In addition, the unique current IKur was suppressed by 1 –50 mM EPA (IC50: 11.3 mM) and DHA (IC50: 3.5 mM) in human atrial cells. Moreover, EPA and DHA also reduced INa in human atrial myocytes in a concentration-dependent manner (IC50: 10.7 mM for EPA; 13.7 mM for DHA), negatively shifted the potential of INa availability, and slowed recovery of INa from inactivation. Conclusions: The present study demonstrates the novel information that EPA and DHA inhibit Ito, IKur, and INa in human atrial myocytes in a concentration-dependent manner, and these effects likely contribute at least in part to anti-atrial fibrillation of n-3 PUFAs in humans.