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.
Bogdanov
K Y
KY
Laboratory of Heart Electrophysiology, Cardiology Research Center, Moscow, Russia.
Spurgeon
H A
HA
Vinogradova
T M
TM
Lakatta
E G
EG
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D004553:Electric Conductivity; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D019787:Linoleic Acid / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D015221:Potassium Channels; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D019787:Linoleic Acid; D015118:Eicosapentaenoic Acid