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

Grigori Y. Rychkov, Tom Litjens, Michael L. Roberts, Greg J. Barritt

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Vasopressin 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) Ca 2+inflow through SOCs (ISOC) initiated by intracellular application of Ins(1,4,5)P3 in H4IIE cells. Preincubation 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 [Ca 2+]cyt in liver cells. However, AA may be a physiological modulator of Ca2+ inflow in these cells.

Original languageEnglish
Pages (from-to)551-556
Number of pages6
JournalBiochemical Journal
Volume385
Issue number2
DOIs
Publication statusPublished - 15 Jan 2005

Keywords

  • Arachidonic acid
  • Ca-release-activated Ca channel (CRAC channel)
  • H4IIE liver cell
  • Iso-tetrandrine
  • Patch-clamp recording
  • Store-operated Ca channel

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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