Modulation of the transient outward current in adult rat ventricular myocytes by polyunsaturated fatty acids

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 mu M) all PUFAs except AA inhibited, by similar to 40%, the transient outward current (I-to) without affecting other K+ currents and markedly prolonged the action potential (AP). AA inhibited I-to but also augmented a sustained depolarization-induced outward K+ current (I-sus); 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 mu M) further inhibited I-to and also inhibited I-sus. Thus, at high concentrations, PUFAs have a nonspecific effect on several K+ channels; at low concentrations, PUFAs preferentially inhibit I-to and prolong the AP.