title: Atypical Ca2+-induced Ca2+ release from a sarco-endoplasmic reticulum Ca2+-ATPase 3-dependent Ca2+ pool in mouse pancreatic beta-cells.
abstract: The contribution of Ca(2+) release from intracellular stores to the rise in the free cytosolic Ca(2+) concentration ([Ca(2+)](c)) triggered by Ca(2+) influx was investigated in mouse pancreatic beta-cells. Depolarization of beta-cells by 45 mm K(+) (in the presence of 15 mm glucose and 0.1 mm diazoxide) evoked two types of [Ca(2+)](c) responses: a monotonic and sustained elevation; or a sustained elevation superimposed by a transient [Ca(2+)](c) peak (TCP) (40-120 s after the onset of depolarization). Simultaneous measurements of [Ca(2+)](c) and voltage-dependent Ca(2+) current established that the TCP did not result from a larger Ca(2+) current. Abolition of the TCP by thapsigargin and its absence in sarco-endoplasmic reticulum Ca(2+)-ATPase 3 (SERCA3) knockout mice show that it is caused by Ca(2+) mobilization from the endoplasmic reticulum. A TCP could not be evoked by the sole depolarization of beta-cells but required a rise in [Ca(2+)](c) pointing to a Ca(2+)-induced Ca(2+) release (CICR). This CICR did not involve inositol 1,4,5-trisphosphate (IP(3)) receptors (IP(3)Rs) because it was resistant to heparin. Nor did it involve ryanodine receptors (RyRs) because it persisted after blockade of RyRs with ryanodine, and was not mimicked by caffeine, a RyR agonist. Moreover, RyR1 and RyR2 mRNA were not found and RyR3 mRNA was only slightly expressed in purified beta-cells. A CICR could also be detected in a limited number of cells in response to glucose. Our data demonstrate, for the first time in living cells, the existence of an atypical CICR that is independent from the IP(3)R and the RyR. This CICR is prominent in response to a supraphysiological stimulation with high K(+), but plays little role in response to glucose in non-obese mouse pancreatic beta-cells.
authors.affiliation: Unité d'Endocrinologie et Métabolisme, University of Louvain Faculty of Medicine, Brussels, Belgium.
authors.forename: Melanie C
authors.initials: MC
authors.lastname: Beauvois
authors.forename: Abdelilah
authors.initials: A
authors.lastname: Arredouani
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Jonas
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Rolland
authors.forename: Frans
authors.initials: F
authors.lastname: Schuit
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Henquin
authors.forename: Patrick
authors.initials: P
authors.lastname: Gilon
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D005260:Female; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D012433:Ryanodine / Q000494:pharmacology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
chemical_list: D012433:Ryanodine; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506950:Atp2a3 protein, mouse; D000252:Calcium-Transporting ATPases; D002118:Calcium