Effects of omega-3 polyunsaturated fatty acids on cardiac sarcolemmal Na(+)/H(+) exchange.
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 omega-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 microM eicosapentanoic acid (EPA) or docosahexanoic acid (DHA). H(+)-dependent (22)Na(+) uptake was inhibited by 30-50% after treatment with > or =50 microM EPA or > or =25 microM DHA. This was a specific effect of these PUFAs, because 50 microM 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.
Goel
Danny P
DP
Cell Biology Laboratory, Division of Stroke and Vascular Disease, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba R2H 2A6, Canada.
Maddaford
Thane G
TG
Pierce
Grant N
GN
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D016923:Cell Death / Q000502:physiology; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015118:Eicosapentaenoic Acid; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D013552:Swine
D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D017923:Sodium-Hydrogen Exchangers; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid