Arachidonic acid inhibits the store-operated Ca2+ current in rat liver cells.
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 microM) did inhibit (IC50=2.4+/-0.1 microM) 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.
Rychkov
Grigori Y
GY
School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia 5005, Australia. Grigori.Rychkov@adelaide.edu.au
Litjens
Tom
T
Roberts
Michael L
ML
Barritt
Greg J
GJ
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004594:Electrophysiology / Q000379:methods; D008114:Liver Neoplasms, Experimental / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats
D016718:Arachidonic Acid; D002118:Calcium