Ca2+-Induced Ca2+ Release in the Pancreatic β-Cell: Direct Evidence of Endoplasmic Reticulum Ca2+ Release

The role of the Ca2+-induced Ca2+ release channel (ryanodine receptor) in MIN6 pancreatic β-cells was investigated. An endoplasmic reticulum (ER)-targeted “cameleon” was used to report lumenal free Ca2+. Depolarization of MIN6 cells with KCl led to release of Ca2+ from the ER. This ER Ca2+ release w...

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Bibliographic Details
Published in:Endocrinology (Philadelphia) 2003-08, Vol.144 (8), p.3565-3574
Main Authors: Graves, Thomas K, Hinkle, Patricia M
Format: Article
Language:English
Subjects:
Beta cells
Biological and medical sciences
Caffeine
Calcium (reticular)
Calcium antagonists
Calcium channels (voltage-gated)
Calcium ions
Calcium release channels
Calcium signalling
Channel gating
Choline
Cresols
Depolarization
Endoplasmic reticulum
Fundamental and applied biological sciences. Psychology
Pancreas
Potassium chloride
Receptors
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Summary:The role of the Ca2+-induced Ca2+ release channel (ryanodine receptor) in MIN6 pancreatic β-cells was investigated. An endoplasmic reticulum (ER)-targeted “cameleon” was used to report lumenal free Ca2+. Depolarization of MIN6 cells with KCl led to release of Ca2+ from the ER. This ER Ca2+ release was mimicked by treatment with the ryanodine receptor agonists caffeine and 4-chloro-m-cresol, reversed by voltage-gated Ca2+ channel antagonists and blocked by treatment with antagonistic concentrations of ryanodine. The depolarization-induced rise in cytoplasmic Ca2+ was also inhibited by ryanodine, which did not alter voltage-gated Ca2+ channel activation. Both ER and cytoplasmic Ca2+ changes induced by depolarization occurred in a dose-dependent manner. Glucose caused a delayed rise in cytoplasmic Ca2+ but no detectable change in ER Ca2+. Carbamyl choline caused ER Ca2+ release, a response that was not altered by ryanodine. Taken together, these results provide strong evidence that Ca2+-induced Ca2+ release augments cytoplasmic Ca2+ signals in pancreatic β-cells.
ISSN:0013-7227
1945-7170
DOI:10.1210/en.2002-0104