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1 Laboratory of Heart Electrophysiology, Institute of Experimental Cardiology, Cardiology Research Center, Moscow 121552, Russia; and 2 Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224
With the whole cell patch-clamp technique, we studied the effects of the n-3 and n-6 polyunsaturated fatty acids (PUFAs), linoleic (C18:2n-6), eicosapentaenoic (C20:4n-3), docosahexaenoic (C22:5n-3), and arachidonic (AA; C20:4n-6) acids, on K+ currents in rat ventricular myocytes. At low concentrations (5-10 µM) all PUFAs except AA inhibited, by ~40%, the transient outward current (Ito) without affecting other K+ currents and markedly prolonged the action potential (AP). AA inhibited Ito but also augmented a sustained depolarization-induced outward K+ current (Isus); the latter effect did not occur in the presence of 4-aminopyridine or with eicosatetraynoic acid, a nonmetabolizable analog of AA. Higher concentrations of PUFAs (20-50 µM) further inhibited Ito and also inhibited Isus. Thus, at high concentrations, PUFAs have a nonspecific effect on several K+ channels; at low concentrations, PUFAs preferentially inhibit Ito and prolong the AP.
linoleic acid; eicosapentaenoic acid; fish oil; arachidonic acid; potassium currents
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