Ca(2+)-induced Ca(2+) release in the pancreatic beta-cell: direct evidence of endoplasmic reticulum Ca(2+) release.
The role of the Ca(2+)-induced Ca(2+) release channel (ryanodine receptor) in MIN6 pancreatic beta-cells was investigated. An endoplasmic reticulum (ER)-targeted "cameleon" was used to report lumenal free Ca(2+). Depolarization of MIN6 cells with KCl led to release of Ca(2+) from the ER. This ER Ca(2+) release was mimicked by treatment with the ryanodine receptor agonists caffeine and 4-chloro-m-cresol, reversed by voltage-gated Ca(2+) channel antagonists and blocked by treatment with antagonistic concentrations of ryanodine. The depolarization-induced rise in cytoplasmic Ca(2+) was also inhibited by ryanodine, which did not alter voltage-gated Ca(2+) channel activation. Both ER and cytoplasmic Ca(2+) changes induced by depolarization occurred in a dose-dependent manner. Glucose caused a delayed rise in cytoplasmic Ca(2+) but no detectable change in ER Ca(2+). Carbamyl choline caused ER Ca(2+) release, a response that was not altered by ryanodine. Taken together, these results provide strong evidence that Ca(2+)-induced Ca(2+) release augments cytoplasmic Ca(2+) signals in pancreatic beta-cells.
Graves
Thomas K
TK
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York 14642, USA.
Hinkle
Patricia M
PM
D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D003408:Cresols / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000502:physiology*; D005947:Glucose / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D008564:Membrane Potentials / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D003408:Cresols; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; C006984:chlorocresol; D002110:Caffeine; D011189:Potassium Chloride; D002217:Carbachol; D010738:Type C Phospholipases; D005947:Glucose; D002118:Calcium