Fatty acid augmentation of the cardiac slowly activating delayed rectifier current (IKs) is conferred by hminK.
The mechanism by which dietary fatty acids confer protection against cardiac arrhythmias and sudden cardiac death is not resolved. Here, we study the effects of several known cardio-protective and arrhythmogenic fatty acids on the slowly activating delayed rectifier potassium current (IKs), which is responsible for the repolarization phase of the cardiac action potential. cRNAs encoding either or both of the two subunits, KvLQT1 and hminK, that together produce IKs, were injected into Xenopus oocytes, and the effects of various fatty acids were determined. Docosahexaenoic acid (DHA) significantly augmented IKs as did the short-chained fully saturated lauric acid, and to a lesser extent the cis-unsaturated oleic acid. Eicosapentaenoic acid (EPA) was without significant effect on current magnitude, although it reduced the rate of activation. These results suggest that not all "antiarrhythmic" fatty acids target the same channel. To examine the role of hminK in this response, KvLQT1 was expressed alone. In this case, DHA, lauric acid, and oleic acid did not augment current, suggesting that hminK confers fatty acid sensitivity to IKs.
Department of Physiology, The University of Melbourne, Victoria, 3010, Australia.
Gavin K
GK
Doolan
Rekha G
RG
Panchal
Eva L
EL
Fonnes
Alison L
AL
Clarke
David A
DA
Williams
Steven
S
Petrou
D000818:Animals; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015118:Eicosapentaenoic Acid; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007850:Lauric Acids / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology; D015221:Potassium Channels / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated
D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D007850:Lauric Acids; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C059983:potassium channel protein I(sk); C030358:lauric acid; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid