THE ELECTRICAL AND MECHANICAL RESPONSE OF ADULT GUINEA-PIG AND RAT VENTRICULAR MYOCYTES TO OMEGA-3 POLYUNSATURATED FATTY-ACIDS

Single adult guinea-pig and rat ventricular cardiac myocytes were used to study the effects of two members of the omega 3 class of polyunsat urated fatty acids, docosahexaenoic acid and eicosapentaenoic acid, on the electrical and mechanical activity of cardiac muscle. Docosahexae noic acid and eicosapentaenoic acid reduced the electrical excitabilit y of both guinea-pig and rat cells in a dose-dependent manner. Both ag ents produced a dose-dependent negative inotropic response in guinea-p ig cells but in the rat cells there was first a dose-dependent positiv e inotropic effect at low concentrations (< 10 mu M) followed by a neg ative inotropic effect at higher concentrations (>10 mu M). Possible m echanisms by which these agents affect contraction were studied using conventional electrophysiological techniques. The polyunsaturated fatt y acids reduced the action potential duration and the plateau potentia l of the guinea-pig cells in a simple, dose-dependent manner. In contr ast, the effect on the rat action potential mirrored the inotropic eff ect. At low concentrations (< 10 mu M) there was a concentration-depen dent increase in action potential duration followed by a concentration -dependent decrease at higher concentrations (> 10 mu M). Both polyuns aturated fatty acids decreased the fast Nai current and the L-type Ca2 + current in a concentration-dependent but not use-dependent manner in cells from both species. In the rat cells these agents inhibited the transient outward current resulting in an increase in the duration of the rat action potential. The effects of polyunsaturated fatty acids o n the Ca2+ Na+ and K+ currents underlie these changes in the action po tentials in guinea-pig and rat heart cells. The effects on the L-type Ca2+ current and action potential duration can also explain both the s imple negative inotropic effects of the agents on the guinea-pig cells and the more complex effects on the rat cells. These effects of polyu nsaturated fatty acids on membrane currents may account for their anti -arrhythmic properties. (C) 1998 Elsevier Science B.V. All rights rese rved.