Inhibitory effects of ω-3 polyunsaturated fatty acids on receptor-mediated non-selective cation currents in rat A7r5 vascular smooth muscle cells

Abstract

1. The effects of ω-3 polyunsaturated fatty acids on receptor-mediated non-selective cation current (I(cat)) and KC current were investigated in aortic smooth muscle cells from foetal rat aorta (A7r5 cells). The whole-cell voltage clamp technique was employed. 2. With a K+-containing solution, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA, 30 μM) produced an outward current at a holding potential of -40 mV. This response was inhibited by tetraethylammonium (20 mM) or Cs+ in the patch pipette solution, and the reversal potential of the EPA-induced current followed the K+ equilibrium potential in a near Nernstian manner. 3. Under conditions with a Cs+-containing pipette solution, both vasopressin and endothelin-1 (100 nM) induced a long-lasting inward current at a holding potential of -60 mV. The reversal potential of these agonist-induced currents was about +0 mV, and was not significantly altered by the replacement of the extracellular or intracellular Cl- concentration, suggesting that the induced current was a cation-selective current (I(cat)). 4. La3+ and Cd2+ (1 mM) completely abolished these agonist-induced I(cat), but nifedipine (10 μM) failed to inhibit it significantly. 5. ω-3 polyunsaturated fatty acids (3-100 μM), EPA, DHA and docosapentaenoic acids (DPA), inhibited the agonist-induced I(cat) in a concentration-dependent manner. The potency of the inhibitory effect was EPA > DHA > DPA, and the half maximal inhibitory concentration (IC50) of EPA was about 7 μM. 6. Arachidonic and linoleic acids (10, 30 μM) showed a smaller inhibitory effect compared to ω-3 fatty acids. Also, oleic and stearic acids (30 μM) did not show a significant inhibitory effect on I(cat). 7. A similar inhibitory action of EPA was observed when I(cat) was activated by intracellularly applied GTPγS in the absence of agonists, suggesting that the site of action of ω-3 fatty acids is not located on the receptor. 8. These results demonstrate that ω-3 polyunsaturated fatty acids can activate a K+ current and also effectively inhibit receptor-mediated non-selective cation currents in rat A7r5 vascular smooth muscle cells. Thus, the data suggest that ω-3 fatty acids may play an important role in the regulation of vascular tone.