title: Endoplasmic reticulum calcium store regulates membrane potential in mouse islet beta-cells.
abstract: Glucose stimulation of islet beta-cell insulin secretion is initiated by membrane depolarization and an elevation in intracellular free calcium concentration ([Ca2+]i) from a combination of influx through depolarization-activated Ca2+ channels and intracellular Ca2+ store release. Prevention of Ca2+ store refilling with thapsigargin produced a sustained depolarization, leading to enhanced Ca2+ influx and an elevation in [Ca2+]i in 12 mM glucose. Depletion of intracellular Ca2+ stores by external EGTA reduced [Ca2+]i and also caused a long-lasting depolarization. In single beta-cells, external EGTA activated an inward current, the voltage range and kinetic properties of which differed from those of voltage-dependent Ca2+ channels. A novel pathway thus exists in beta-cells by which depletion of endoplasmic reticulum Ca2+ stores results in the activation of an inward current that, by inducing depolarization, facilitates Ca2+ influx through voltage-gated Ca2+ channels. The physiological relevance of this pathway in the control of beta-cell function is indicated by the stimulation of insulin secretion by thapsigargin.
authors.affiliation: Department of Cell Physiology, Glaxo Research Institute, Research Triangle Park, North Carolina 27709.
authors.forename: J F
authors.initials: JF
authors.lastname: Worley
authors.forename: M S
authors.initials: MS
authors.lastname: McIntyre
authors.forename: B
authors.initials: B
authors.lastname: Spencer
authors.forename: R J
authors.initials: RJ
authors.lastname: Mertz
authors.forename: M W
authors.initials: MW
authors.lastname: Roe
authors.forename: I D
authors.initials: ID
authors.lastname: Dukes
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D004721:Endoplasmic Reticulum / Q000502:physiology*; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D013997:Time Factors
chemical_list: D007328:Insulin; D013729:Terpenes; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D005947:Glucose; D002118:Calcium