Arachidonic acid inhibits the store-operated Ca2+ current in rat liver cells

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dc.contributor.authorRychkov, G.
dc.contributor.authorLitjens, T.
dc.contributor.authorRoberts, M.
dc.contributor.authorBarritt, G.
dc.date.issued2005
dc.descriptionCopyright © 2005 The Biochemical Society
dc.description.abstractVasopressin and other phospholipase-C-coupled hormones induce oscillations (waves) of [Ca2+]cyt (cytoplasmic Ca2+ concentration) in liver cells. Maintenance of these oscillations requires replenishment of Ca2+ in intracellular stores through Ca2+ inflow across the plasma membrane. While this may be achieved by SOCs (store-operated Ca2+ channels), some studies in other cell types indicate that it is dependent on AA (arachidonic acid)-activated Ca2+ channels. We studied the effects of AA on membrane conductance of rat liver cells using whole-cell patch clamping. We found no evidence that concentrations of AA in the physiological range could activate Ca2+-permeable channels in either H4IIE liver cells or rat hepatocytes. However, AA (1–10 µM) did inhibit (IC50=2.4±0.1 µM) Ca2+ inflow through SOCs (ISOC) initiated by intracellular application of Ins(1,4,5)P3 in H4IIE cells. Pre-incubation with AA did not inhibit ISOC development, but decreased maximal amplitude of the current. Iso-tetrandrine, widely used to inhibit receptor-activation of phospholipase A2, and therefore AA release, inhibited ISOC directly in H4IIE cells. It is concluded that (i) in rat liver cells, AA does not activate an AA-regulated Ca2+-permeable channel, but does inhibit SOCs, and (ii) iso-tetrandrine and tetrandrine are effective blockers of CRAC (Ca2+-release-activated Ca2+) channel-like SOCs. These results indicate that AA-activated Ca2+-permeable channels do not contribute to hormone-induced increases or oscillations in [Ca2+]cyt in liver cells. However, AA may be a physiological modulator of Ca2+ inflow in these cells.
dc.description.statementofresponsibilityGrigori Y. Rychkov, Tom Litjens, Michael L. Roberts and Greg J. Barritt
dc.identifier.citationBiochemical Journal, 2005; 385(2):551-556
dc.identifier.doi10.1042/BJ20041604
dc.identifier.issn0264-6021
dc.identifier.issn1470-8728
dc.identifier.orcidRychkov, G. [0000-0002-2788-2977]
dc.identifier.urihttp://hdl.handle.net/2440/27473
dc.language.isoen
dc.publisherPortland Press
dc.source.urihttps://doi.org/10.1042/bj20041604
dc.subjectarachidonic acid
dc.subjectCa2+-release-activated Ca2+ channel (CRAC channel)
dc.subjectH4IIE liver cell
dc.subjectiso-tetrandrine
dc.subjectpatch-clamp recording
dc.subjectstore-operated Ca2+ channel
dc.titleArachidonic acid inhibits the store-operated Ca2+ current in rat liver cells
dc.typeJournal article
pubs.publication-statusPublished

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