EXTERNAL BLOCKADE OF THE MAJOR CARDIAC DELAYED-RECTIFIER K-ACIDS( CHANNEL (KV1.5) BY POLYUNSATURATED FATTY)

The present work shows that arachidonic acid and some other long chain polyunsaturated fatty acids; such as docosahexaenoic acid, which is a bundant in fish oil, produce a direct open channel block of the major voltage-dependent K+ channel (Kv1.5) cloned in cardiac cells. The inhi bitory action of these selected fatty acids is seen when they are appl ied extracellularly but not when they are included in the patch pipett e. Fatty acids then appear to bind to an external site on the Kv1.5 ch annel structure. Inhibition of Kv1.5 channel activity by polyunsaturat ed fatty acids (acceleration of the apparent inactivation and decrease of the peak current) is similar to that produced by the class III ant iarrhythmic tedisamil. Docosahexaenoic acid and arachidonic acid also inhibit the delayed-rectifier K+ channel currents in cultured mouse an d rat cardiomyocytes. These results are discussed in the light of the reported fatty acids effects on cardiac function in diseased states. S ince Kv1.5 is also present in the brain, the results reported here cou ld also have a significance in terms of processes such as long-term po tentiation or depression.