title: No evidence for a role of reverse Na(+)-Ca2+ exchange in insulin release from mouse pancreatic islets.
abstract: We studied whether reverse Na(+)-Ca2+ exchange can increase cytoplasmic Ca2+ ([Ca2+]i) in mouse islets and contribute to insulin release. The exchange was stimulated by replacing Na+ with choline, sucrose, or lithium in a medium containing 15 mM glucose. Na+ omission increased electrical activity in B cells, [Ca2+]i, and insulin release. When voltage-dependent Ca2+ channels were blocked by nimodipine or closed by holding the membrane polarized with diazoxide, Na+ omission caused a slight hyperpolarization, a small rise in [Ca2+]i, and a marginal increase in insulin release (the latter only with choline). This small rise in [Ca2+]i was dependent on extracellular Ca2+ but was hardly augmented when intracellular Na+ was raised with alanine. When B cells were depolarized by 30 mM K+, Na+ omission did not affect the membrane potential but increased [Ca2+]i and insulin release. If Ca2+ channels were blocked by nimodipine, only marginal increases in Ca2+ and insulin release persisted, which were not different from those observed when the cells were not depolarized. This indicates that Ca2+ influx through voltage-dependent Ca2+ channels rather than via reverse Na(+)-Ca2+ exchange underlies the rise in [Ca2+]i and in insulin release produced by Na+ removal. No decisive support for Ca2+ influx by reverse Na(+)-Ca2+ exchange could be found.
authors.affiliation: Unité d'Endocrinologie et Métabolisme, University of Louvain School of Medicine, Brussels, Belgium.
authors.forename: M J
authors.initials: MJ
authors.lastname: Garcia-Barrado
authors.forename: P
authors.initials: P
authors.lastname: Gilon
authors.forename: Y
authors.initials: Y
authors.lastname: Sato
authors.forename: M
authors.initials: M
authors.lastname: Nenquin
authors.forename: J C
authors.initials: JC
authors.lastname: Henquin
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D046508:Culture Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D017136:Ion Transport; D007515:Islets of Langerhans / Q000502:physiology*; D008564:Membrane Potentials; D051379:Mice; D012964:Sodium / Q000378:metabolism*
chemical_list: D007328:Insulin; D012964:Sodium; D002118:Calcium