Atypical Ca2+-induced Ca2+ release from a sarco-endoplasmic reticulum Ca2+-ATPase 3-dependent Ca2+ pool in mouse pancreatic β-cells

Melanie C. Beauvois, Abdelilah Arredouani, Jean Christophe Jonas, Jean François Rolland, Frans Schuit, Jean Claude Henquin, Patrick Gilon

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The contribution of Ca2+ release from intracellular stores to the rise in the free cytosolic Ca2+ concentration ([Ca2+]c) triggered by Ca2+ influx was investigated in mouse pancreatic β-cells. Depolarization of β-cells by 45 mM K+ (in the presence of 15 mM glucose and 0.1 mM diazoxide) evoked two types of [Ca2+]c responses: a monotonic and sustained elevation; or a sustained elevation superimposed by a transient [Ca2+]c peak (TCP) (40-120 s after the onset of depolarization). Simultaneous measurements of [Ca2+]c and voltage-dependent Ca2+ current established that the TCP did not result from a larger Ca2+ current. Abolition of the TCP by thapsigargin and its absence in sarco-endoplasmic reticulum Ca2+-ATPase 3 (SERCA3) knockout mice show that it is caused by Ca2+ mobilization from the endoplasmic reticulum. A TCP could not be evoked by the sole depolarization of β-cells but required a rise in [Ca2+]c pointing to a Ca2+-induced Ca2+ release (CICR). This CICR did not involve inositol 1,4,5-trisphosphate IP3) receptors (IP3Rs) 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 β-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 IP3R 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 β-cells.

Original languageEnglish
Pages (from-to)141-156
Number of pages16
JournalJournal of Physiology
Issue number1
Publication statusPublished - 15 Aug 2004


ASJC Scopus subject areas

  • Physiology

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