title: Membrane potential and cytosolic free calcium levels modulate acetylcholine-induced inositol phosphate production in insulin-secreting BTC3 cells.
abstract: Effects of membrane potential and cytosolic free Ca2+ concentrations ([Ca2+]i) on acetycholine (ACh)-induced inositol phosphate production were investigated in insulin secreting betaTC3 cells. ACh (10 microM) caused a rapid inositol 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 diazoxide, 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-induced changes in membrane potential and [Ca2+]i play an important role in controlling Ins(1,4,5)P3 production in insulin-secreting betaTC3 cells.
authors.affiliation: Department of Medical Physiology, The Panum Institute, University of Copenhagen, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Gromada
authors.forename: S
authors.initials: S
authors.lastname: Dissing
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism*; D004533:Egtazic Acid / Q000031:analogs & derivatives; D004789:Enzyme Activation; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D007328:Insulin / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D008564:Membrane Potentials; D051379:Mice; D011976:Receptors, Muscarinic / Q000187:drug effects; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D007328:Insulin; D011976:Receptors, Muscarinic; D004533:Egtazic Acid; D015759:Ionomycin; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D000109:Acetylcholine; D002118:Calcium