Arachidonic acid stimulates extracellular Ca2+ entry in rat pancreatic β cells via activation of the noncapacitative arachidonate-regulated Ca2+ (ARC) channels

Abstract

Arachidonic acid (AA) is generated in the pancreatic islets during glucose stimulation. We investigated whether AA activated extracellular Ca2+ entry in rat pancreatic β cells via a pathway that was independent of the activation of voltage-gated Ca2+ channels. The AA triggered [Ca2+]i rise did not involve activation of GPR40 receptors or AA metabolism. When cells were voltage clamped at −70mV, the AA-mediated intracellular Ca2+ release was accompanied by extracellular Ca2+ entry. AA accelerated the rate of Mn2+ quench of indo-1 fluorescence (near the Ca2+-independent wavelength of indo-1), reflecting the activation of a Ca2+-permeable pathway. The AA-mediated acceleration of Mn2+ quench was inhibited by La3+ but not by 2-APB (a blocker of capacitative Ca2+ entry), suggesting the involvement of arachidonate-regulated Ca2+ (ARC) channels. Consistent with this, intracellular application of the charged membrane-impermeant analog of AA, arachidonyl-coenzyme A (ACoA) triggered extracellular Ca2+ entry, as well as the activation of a La3+-sensitive small inward current (1.7pA/pF) at −70mV. Our results indicate that the activation of ARC channels by intracellular AA triggers extracellular Ca2+ entry. This action may contribute to the effects of AA on Ca2+ signals and insulin secretion in rat β cells.