Effects of polyunsaturated fatty acids on cardiac voltage-activated K~+ currents in adult ferret cardiomyocytes

This stud was carried out in adult ferret cardiomyocytes to investigate the effects of the n-3 polyunsaturated fatty acids (PUFAs) on voltage-gated K~+ currents. We report that the two outward K~+ current: the transient outward K~+ current (I_(to)) and the delayed rectifier K~+ current (I_K), are both inhibited by the n-3 PUFAs, while the inwardly rectifying K~+ current (I_(K1)) is unaffected by the n-3 PUFAs. Docosahexaenoic acid (C22: 6n-3, DHA) produced a concentration-dependent suppression of I_(to) and I_K in adult ferret cardiomyocytes with an IC_(50) of 7.5 and 20 μmol/L, respectively; but not I_(K1). In addition, eicosapentaenoic acid (C20: 5n-3, EPA) had the effects on the three K~+ channels similar to DHA. Arachidonic acid (C20: 4n-6, AA) at 5 or 10 μmol/L, after an initial inhibitory effect on I_K, caused an activation of I_(K,AA) which was prevented by pretreatment with indomethacin, a cyclooxygenase inhibitor. Monounsaturated and saturated fatty acids, which are not atiarrhythmic, lack the effects on these K~+ currents. Our results demonstrate that the n-3 PUFAs inhibit cardiac I_(to) and I_K with much less potency compared to their effects on cardiac Na~+ and Ca~(2+) currents as we reported previously. This inhibition of the cardiac ion currents by the n-3 PUFAs may contribute to their antiarrhythmic actions.