Membrane potential and cytosolic free calcium levels modulate acetylcholine-indueed inositol phosphate production in insulin-secreting BTC3 cells

摘要

Effects of membrane potential and cytosolic free Ca2+ concentrations ([Ca2+]i) on acetycholine (ACh)-induced inositol phosphate production were investigated in insulin secreting TC3 cells. Ach (10M) caused a rapid insitol 1, 4, 5-trisphosphate (ins(1, 4, 5)P3) production and increase in [Ca2+]i reaching a maximum within 5 s. The rise in Ins(1, 4, 5)P3 production was reduced by 79±5% when [Ca2+]i was kept low in cells loaded with the Ca2+ chelator BAPTA. The ACh-evoked Ins (1, 4, 5)P3 production also depended on the membrane potential as it was reduced by 31±6% in cells hyperpolarized by diazxide, an opener of ATP-sensitive K+ channels. The Ca2+ ionophore ionomycin caused a rapid increase in [Ca2+]i and in the cellular Ins (1, 4, 5)P3 content. We conclude that stimulation-in-duced changes in membrane potential and [Ca2+]i play an important role in controlling Ins (1, 4, 5)P3 production in insulin-secreting TC3 cells.