title: Arachidonic acid stimulates extracellular Ca(2+) entry in rat pancreatic beta cells via activation of the noncapacitative arachidonate-regulated Ca(2+) (ARC) channels.
abstract: Arachidonic acid (AA) is generated in the pancreatic islets during glucose stimulation. We investigated whether AA activated extracellular Ca(2+) entry in rat pancreatic beta cells via a pathway that was independent of the activation of voltage-gated Ca(2+) channels. The AA triggered [Ca(2+)](i) rise did not involve activation of GPR40 receptors or AA metabolism. When cells were voltage clamped at -70mV, the AA-mediated intracellular Ca(2+) release was accompanied by extracellular Ca(2+) entry. AA accelerated the rate of Mn(2+) quench of indo-1 fluorescence (near the Ca(2+)-independent wavelength of indo-1), reflecting the activation of a Ca(2+)-permeable pathway. The AA-mediated acceleration of Mn(2+) quench was inhibited by La(3+) but not by 2-APB (a blocker of capacitative Ca(2+) entry), suggesting the involvement of arachidonate-regulated Ca(2+) (ARC) channels. Consistent with this, intracellular application of the charged membrane-impermeant analog of AA, arachidonyl-coenzyme A (ACoA) triggered extracellular Ca(2+) entry, as well as the activation of a La(3+)-sensitive small inward current (1.7pA/pF) at -70mV. Our results indicate that the activation of ARC channels by intracellular AA triggers extracellular Ca(2+) entry. This action may contribute to the effects of AA on Ca(2+) signals and insulin secretion in rat beta cells.
authors.affiliation: Centre for Neuroscience, University of Alberta, Edmonton, Canada.
authors.forename: Valerie
authors.initials: V
authors.lastname: Yeung-Yam-Wah
authors.forename: Andy K
authors.initials: AK
authors.lastname: Lee
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Tse
authors.forename: Amy
authors.initials: A
authors.lastname: Tse
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D001896:Boron Compounds / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007811:Lanthanum / Q000494:pharmacology; D008297:Male; D008345:Manganese / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000214:Acyl Coenzyme A; D001896:Boron Compounds; D002121:Calcium Channel Blockers; D015220:Calcium Channels; C026563:arachidonyl-coenzyme A; D016718:Arachidonic Acid; D008345:Manganese; D007811:Lanthanum; C109986:2-aminoethoxydiphenyl borate; D005947:Glucose