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Atypical Ca 2+ ‐induced Ca 2+ release from a sarco‐endoplasmic reticulum Ca 2+ ‐ATPase 3‐dependent Ca 2+ pool in mouse pancreatic β‐cells
Author(s) -
Beauvois Melanie C.,
Arredouani Abdelilah,
Jonas JeanChristophe,
Rolland JeanFrançois,
Schuit Frans,
Henquin JeanClaude,
Gilon Patrick
Publication year - 2004
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2004.067454
Subject(s) - endoplasmic reticulum , ryanodine receptor , thapsigargin , depolarization , endocrinology , medicine , chemistry , inositol , cyclopiazonic acid , biophysics , receptor , biology , biochemistry
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 β‐cells. Depolarization of β‐cells by 45 m m K + (in the presence of 15 m m glucose and 0.1 m m 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 β‐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 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 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 β‐cells.