title: Crosstalk between membrane potential and cytosolic Ca2+ concentration in beta cells from Sur1-/- mice.
abstract: OBJECTIVE
  Islets or beta cells from Sur1(-/-) mice were used to determine whether changes in plasma membrane potential (V(m)) remain coupled to changes in cytosolic Ca(2+) ([Ca(2+)](i)) in the absence of K(ATP) channels and thus provide a triggering signal for insulin secretion. The study also sought to elucidate whether [Ca(2+)](i) influences oscillations in V(m) in sur1(-/-) beta cells.
  
  
  METHODS
  Plasma membrane potential and ion currents were measured with microelectrodes and the patch-clamp technique. [Ca(2+)](i) was monitored with the fluorescent dye fura-2. Insulin secretion from isolated islets was determined by static incubations.
  
  
  RESULTS
  Membrane depolarisation of Sur1(-/-) islets by arginine or increased extracellular K(+), elevated [Ca(2+)](i) and augmented insulin secretion. Oligomycin completely abolished glucose-stimulated insulin release from Sur1(-/-) islets. Oscillations in V(m) were influenced by [Ca(2+)](i) as follows: (1) elevation of extracellular Ca(2+) lengthened phases of membrane hyperpolarisation; (2) simulating a burst of action potentials induced a Ca(2+)-dependent outward current that was augmented by increased Ca(2+) influx through L-type Ca(2+) channels; (3) Ca(2+) depletion of intracellular stores by cyclopiazonic acid increased the burst frequency in Sur1(-/-) islets, elevating [Ca(2+)](i) and insulin secretion; (4) store depletion activated a Ca(2+) influx that was not inhibitable by the L-type Ca(2+) channel blocker D600.
  
  
  CONCLUSIONS
  Although V(m) is largely uncoupled from glucose metabolism in the absence of K(ATP) channels, increased electrical activity leads to elevations of [Ca(2+)](i) that are sufficient to stimulate insulin secretion. In Sur1(-/-) beta cells, [Ca(2+)](i) exerts feedback mechanisms on V(m) by activating a hyperpolarising outward current and by depolarising V(m) via store-operated ion channels.
authors.affiliation: Department of Pharmacology, Institute of Pharmacy, University of Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Haspel
authors.forename: P
authors.initials: P
authors.lastname: Krippeit-Drews
authors.forename: L
authors.initials: L
authors.lastname: Aguilar-Bryan
authors.forename: J
authors.initials: J
authors.lastname: Bryan
authors.forename: G
authors.initials: G
authors.lastname: Drews
authors.forename: M
authors.initials: M
authors.lastname: Düfer
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000172:deficiency / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying / Q000172:deficiency / Q000235:genetics*; D011955:Receptors, Drug / Q000172:deficiency / Q000235:genetics*; D064233:Sulfonylurea Receptors
chemical_list: D018528:ATP-Binding Cassette Transporters; C577508:Abcc8 protein, mouse; D007211:Indoles; D007328:Insulin; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D001120:Arginine; D011188:Potassium; D002118:Calcium; C000543:cyclopiazonic acid