Effects of polyunsaturated fatty acids on cardiac voltage-activated K(+) currents in adult ferret cardiomyocytes  .
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 (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 micromol/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 micromol/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 antiarrhythmic, 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.
Stem Cell Research Laboratory, Beth Israel Deaconess Medical Center; Massachusetts General Hospital; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA. yxiao@caregroup.harvard.edu
Yong-Fu
YF
Xiao
James P
JP
Morgan
Alexander
A
Leaf
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005289:Ferrets; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*
D024642:Potassium Channels, Voltage-Gated; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid