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 microM) all PUFAs except AA inhibited, by approximately 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 (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 microM) further inhibited I(to) and also inhibited Isus. 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.