Eicosapentaenoic acid triggers Ca release and Ca influx in mouse cerebral cortex endothelial bEND.3 cells.

Eicosapentaenoic acid (EPA), an omega-3 fatty acid abundant in fish oil, protects endothelial cells (EC) from lipotoxicity and triggers EC NO release. The latter is related to an elevation of cytosolic Ca. Although EPA has been shown to cause human EC cytosolic Ca elevation, the mechanism is unclear. Microfluorimetric imaging was used here to measure free cytosolic Ca concentration. EPA was shown to cause intracellular Ca release in mouse cerebral cortex endothelial bEND.3 cells; interestingly, the EPA-sensitive intracellular Ca pool(s) appeared to encompass and was larger than the Ca pool mobilized by sarcoplasmic-endoplasmic reticulum Ca-ATPase inhibition by cyclopiazonic acid. EPA also opened a Ca influx pathway pharmacologically distinct from store-operated Ca influx. Surprisingly, EPA-triggered Ca influx was Ni-insensitive; and EPA did not trigger Mn influx. Further, EPA-triggered Ca influx did not involve Na-Ca exchangers. Thus, our results suggest EPA triggered unusual mechanisms of Ca release and Ca influx in EC.