Termination of asynchronous contractile activity in rat atrial myocytes by n-3 polyunsaturated fatty acids.
A protective effect of the n-3 polyunsaturated fatty acids (PUFAs) in preventing ventricular fibrillation in experimental animals and cultured cardiomyocytes has been demonstrated in a number of studies. In this study, a possible role for the n-3 PUFAs in the treatment of atrial fibrillation (AF) was investigated at the cellular level using atrial myocytes isolated from young adult rats as the experimental model. Electrically-stimulated, synchronously-contracting myocytes were induced to contract asynchronously by the addition of 10 microM isoproterenol. Asynchronous contractile activity was reduced following acute addition of the n-3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) at 10 microM, compared with no fatty acid addition (from 99.0+/-1.0% to 30.7+/-5.2% (p < 0.05) for DHA and 23.8+/-2.8% (p < 0.01) for EPA), while the saturated fatty acid, docosanoic acid (DA) and the methyl ester of DHA (DHA m.e.) did not exert a significant effect on asynchronous contractile activity. Asynchronous contractile activity was also reduced to 1.7+/-1.7% in the presence of the membrane fluidising agent, benzyl alcohol (p < 0.001 vs no fatty acid addition). Cell membrane fluidity was determined by steady state fluorescence anisotropy using the fluorescent probe, TMAP-DPH. Addition of DHA, EPA or benzyl alcohol significantly increased sarcolemmal membrane fluidity (decreased anisotropy, r(ss)) of atrial myocytes compared with no addition of fatty acid (control) (from r(ss) = 0.203+/-0.004 to 0.159+/-0.004 (p < 0.01) for DHA, 0.166+/-0.001 (p < 0.01) for EPA and 0.186+/-0.003 (p < 0.05) for benzyl alcohol, while DA and DHA m.e. were without effect. It is concluded that the n-3 PUFAs exert anti-asynchronous effects in rat atrial myocytes by a mechanism which may involve changes in membrane fluidity.
Jahangiri
A
A
Department of Physiology, The University of Adelaide, SA, Australia.
Leifert
W R
WR
Patten
G S
GS
McMurchie
E J
EJ
D000818:Animals; D001281:Atrial Fibrillation / Q000139:chemically induced* / Q000188:drug therapy; D019905:Benzyl Alcohol / Q000494:pharmacology; D002304:Cardiac Pacing, Artificial; D002470:Cell Survival; D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005454:Fluorescence Polarization; D006325:Heart Atria / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects*; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000502:physiology
D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D007545:Isoproterenol; D019905:Benzyl Alcohol