Abstract

Effects of membrane potential and cytosolic free Ca 2+ concentrations ([Ca 2+] i) on acetycholine (ACh)-induced inositol phosphate production were investigated in insulin secreting βTC3 cells. ACh (10 μM) caused a rapid inositol 1,4,5-trisphosphate (Ins(1,4,5)P 3) production and increase in [Ca 2+] i reaching a maximum within 5 s. The rise in Ins(1,4,5)P 3 production was reduced by 79 ± 5% when [Ca 2+] i was kept low in cells loaded with the Ca 2+ chelator BAPTA. The ACh-evoked Ins(1,4,5)P 3 production also depended on the membrane potential as it was reduced by 31 ± 6% in cells hyperpolarized by diazoxide, an opener of ATP-sensitive K + channels. The Ca 2+ ionophore ionomycin caused a rapid increase in [Ca 2+] i and in the cellular Ins(1,4,5)P 3 content. We conclude that stimulation-induced changes in membrane potential and [Ca 2+] i play an important role in controlling Ins(1,4,5)P 3 production in insulin-secreting βTC3 cells.

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