Eicosapentaenoic acid triggers Ca²⁺ release and Ca²⁺ 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 Ca²⁺. Although EPA has been shown to cause human EC cytosolic Ca²⁺ elevation, the mechanism is unclear. Microfluorimetric imaging was used here to measure free cytosolic Ca²⁺ concentration. EPA was shown to cause intracellular Ca²⁺ release in mouse cerebral cortex endothelial bEND.3 cells; interestingly, the EPA-sensitive intracellular Ca²⁺ pool(s) appeared to encompass and was larger than the Ca²⁺ pool mobilized by sarcoplasmic-endoplasmic reticulum Ca²⁺-ATPase inhibition by cyclopiazonic acid. EPA also opened a Ca²⁺ influx pathway pharmacologically distinct from store-operated Ca²⁺ influx. Surprisingly, EPA-triggered Ca²⁺ influx was Ni²⁺-insensitive; and EPA did not trigger Mn²⁺ influx. Further, EPA-triggered Ca²⁺ influx did not involve Na⁺–Ca²⁺ exchangers. Thus, our results suggest EPA triggered unusual mechanisms of Ca²⁺ release and Ca²⁺ influx in EC.