The goal of this study was to determine the mechanisms of n-3 polyunsaturated fatty acids (n-3 PUFA) on anti-arrhythmias and prevention of sudden death. The calcium-tolerant Sprague-Dawley rat ventricular myocytes were isolated by enzyme digestion. Effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on action potentials and transient outward potassium currents (I (to)) of epicardial ventricular myocytes were investigated using whole-cell patch clamp techniques. Action potential durations (APDs) and I (to) were observed in different concentrations of DHA and EPA. APD(25), APD(50), and APD(90) with 0.1 mu mol/L DHA and EPA were prolonged less than 15% and 10%. However, APDs were prolonged in concentration-dependent manners when DHA and EPA were more than 1 mu mol/L. APD(25), APD(50), and APD(90) were 7.7 +/- A 2.0, 21.2 +/- A 3.5, and 100.1 +/- A 9.8 ms respectively with 10 mu mol/L DHA, and 7.2 +/- A 2.5, 12.8 +/- A 4.2, and 70.5 +/- A 10.7 ms respectively with 10 mu mol/L EPA. I (to) currents were gradually reduced with the increased concentrations of DHA and EPA from 1 to 100 mu mol/L, and their half-inhibited concentrations were 2.3 +/- A 0.2 and 3.8 +/- A 0.6 mu mol/L. The results showed APDs were prolonged and I (to) current densities were gradually reduced with the increased concentrations of DHA and EPA. The anti-arrhythmia mechanisms of n-3 PUFA are complex, however, the effects of n-3 PUFA on action potentials and I (to) may be one of the important mechanisms.