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 μM) did inhibit (IC₅₀=2.4±0.1 μM) Ca²⁺ inflow through SOCs (I_SOC) initiated by intracellular application of Ins(1,4,5)P₃ in H4IIE cells. Pre-incubation with AA did not inhibit I_SOC development, but decreased maximal amplitude of the current. Iso-tetrandrine, widely used to inhibit receptor-activation of phospholipase A₂, and therefore AA release, inhibited I_SOC 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.