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

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Author:
()
James P.MORGAN()
Alexander LEAF()
Journal Title:
ACTA PHYSIOLOGICA SINICA
Issue:
Volume 54, Issue 04, 2002
DOI:
Key Word:
cardiomyocytes;potassium channels;arrhythmia;polyunsaturated fatty acids

Abstract: This study 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+ currents: the transient outward K+ current (Ito) and the delayed rectifier K+ current (IK), are both inhibited by the n-3 PUFAs, while the inwardly rectifying K+ current (IK1) is unaffected by the n-3 PUFAs. Docosahexaenoic acid (C22:6n-3, DHA) produced a concentration-dependent suppression of Ito and IK in adult ferret cardiomyocytes with an IC50 of 7.5 and 20 μmol/L, respectively; but not IK1. 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 IK, caused an activation of IK,AA which was prevented by pretreatment with indomethacin, a cyclooxygenase inhibitor. Monounsaturated and saturated fatty acids, which are not antiarrhythmic, lack the effects on these K+ currents. Our results demonstrate that the n-3 PUFAs inhibit cardiac Ito and IK with much less potency compared to their effects on cardiac Na+ and Ca2+ currents as we reported previously. This inhibition of the cardiac ion currents by the n-3 PUFAs may contribute to their antiarrhythmic actions.

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