External blockade of the major cardiac delayed-rectifier K+ channel (Kv1.5) by polyunsaturated fatty acids.

The present work shows that arachidonic acid andsome other long chain polyunsaturated fatty acids such as docosahexaenoic acid,which is abundant in fish oil, produce a direct open channel block of the majorvoltage-dependent K+ channel (Kv1.5) cloned in cardiac cells. The inhibitoryaction of these selected fatty acids is seen when they are appliedextracellularly but not when they are included in the patch pipette. Fatty acidsthen appear to bind to an external site on the Kv1.5 channel structure.Inhibition of Kv1.5 channel activity by polyunsaturated fatty acids(acceleration of the apparent inactivation and decrease of the peak current) issimilar to that produced by the class III antiarrhythmic tedisamil.Docosahexaenoic acid and arachidonic acid also inhibit the delayed-rectifier K+channel currents in cultured mouse and rat cardiomyocytes. These results arediscussed in the light of the reported fatty acids effects on cardiac functionin diseased states. Since Kv1.5 is also present in the brain, the resultsreported here could also have a significance in terms of processes such aslong-term potentiation or depression.