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 language | English |
---|---|
Pages (from-to) | 551-556 |
Number of pages | 6 |
Journal | Biochemical Journal |
Volume | 385 |
Issue number | 2 |
DOIs | |
Publication status | Published or Issued - 15 Jan 2005 |
Externally published | Yes |
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