title: Coincidence of early glucose-induced depolarization with lowering of cytoplasmic Ca2+ in mouse pancreatic beta-cells.
abstract: 1. The temporal relationship between the early glucose-induced changes of membrane potential and cytoplasmic Ca2+ concentration ([Ca2+]i) was studied in insulin-releasing pancreatic beta-cells. 2. The mean resting membrane potential and [Ca2+]i were about -70 mV and 60 nM, respectively, in 3 mM glucose. 3. Elevating the glucose concentration to 8-23 mM typically elicited a slow depolarization, which was paralleled by a lowering of [Ca2+]i. When the slow depolarization had reached a threshold of -55 to -40 mV, there was rapid further depolarization to a plateau with superimposed action potentials, and [Ca2+]i increased dramatically. 4. Imposing hyperpolarizations and depolarizations of 10 mV from a holding potential of -70 mV had no detectable effect on [Ca2+]i. Furthermore, glucose elevation elicited a decrease in [Ca2+]i even at a holding potential of -70 mV. 5. Step depolarizations induced [Ca2+]i transients, which decayed with time courses well fitted by double exponentials. The slower component became faster by a factor of about 4 upon elevation of glucose, suggesting involvement of ATP-dependent Ca2+ sequestration or extrusion of [Ca2+]i. 6. Glucose stimulation increased the size and accelerated the recovery of carbachol-triggered [Ca2+]i transients, and thapsigargin, an intracellular Ca(2+)-ATPase inhibitor, counteracted the glucose-induced lowering of [Ca2+]i, indicating that calcium transport into intracellular stores is involved in glucose-induced lowering of [Ca2+]i. 7. The results support the notion that in beta-cells, nutrient-induced elevation of ATP leads initially to ATP-dependent removal of Ca2+ from the cytoplasm, paralleled by a slow depolarization due to inhibition of ATP-sensitive K+ channels. Only after depolarization has reached a threshold do action potentials occur, inducing a sharp elevation in [Ca2+]i.
authors.affiliation: Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: R H
authors.initials: RH
authors.lastname: Chow
authors.forename: P E
authors.initials: PE
authors.lastname: Lund
authors.forename: S
authors.initials: S
authors.lastname: Löser
authors.forename: U
authors.initials: U
authors.lastname: Panten
authors.forename: E
authors.initials: E
authors.lastname: Gylfe
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007651:Keto Acids / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
chemical_list: D007651:Keto Acids; D013729:Terpenes; D019284:Thapsigargin; C013082:alpha-ketoisocaproic acid; D002217:Carbachol; D000252:Calcium-Transporting ATPases; D005947:Glucose; D002118:Calcium