Effects of ω-3 polyunsaturated fatty acids on cardiac sarcolemmal Na+/H+ exchange

Abstract

Myocardial ischemia-reperfusion activates the Na+/H+ exchanger, which induces arrhythmias, cell damage, and eventually cell death. Inhibition of the exchanger reduces cell damage and lowers the incidence of arrhythmias after ischemia-reperfusion. The ω-3 polyunsaturated fatty acids (PUFAs) are also known to be cardioprotective and antiarrhythmic during ischemia-reperfusion challenge. Some of the action of PUFAs may occur via inhibition of the Na+/H+ exchanger. The purpose of our study was to determine the capacity for selected PUFAs to alter cardiac sarcolemmal (SL) Na+/H+exchange. Cardiac membranes highly enriched in SL vesicles were exposed to 10–100 μM eicosapentanoic acid (EPA) or docosahexanoic acid (DHA). H+-dependent 22Na+ uptake was inhibited by 30–50% after treatment with ≥50 μM EPA or ≥25 μM DHA. This was a specific effect of these PUFAs, because 50 μM linoleic acid or linolenic acid had no significant effect on Na+/H+ exchange. The SL vesicles did not exhibit an increase in passive Na+ efflux after PUFA treatment. In conclusion, EPA and DHA can potently inhibit cardiac SL Na+/H+ exchange at physiologically relevant concentrations. This may explain, in part, their known cardioprotective effects and antiarrhythmic actions during ischemia-reperfusion.