Voltage-dependent intracellular calcium release from mouse islets stimulated by glucose.
Glucose-activated beta-cell insulin secretion depends upon elevation of intracellular calcium concentration, [Ca2+]i, which is thought to arise from Ca2+ influx through voltage-dependent calcium channels. Using fura-2-loaded mouse islets, we demonstrate, in fact, that the major component of the glucose-activated [Ca2+]i rise represents voltage-dependent intracellular Ca2+ release. Furthermore, the Ca2+ release pool possesses a novel pharmacology in that it is caffeine-sensitive but ryanodine-insensitive. In the absence of external Ca2+, glucose still caused intracellular Ca2+ release, an effect blockable by tetrodotoxin. However, depolarization of the islet with KCl in low Ca(2+)-containing solutions induced intracellular Ca2+ release, which was resistant to tetrodotoxin. We conclude that glucose release of intracellular Ca2+ is dependent upon depolarization alone, possibly through increasing inositol 1,4,5-trisphosphate production.
Department of Cell Physiology and Immunology, Glaxo Research Institute, Research Triangle Park, North Carolina 27709.
M W
MW
Roe
M E
ME
Lancaster
R J
RJ
Mertz
J F
JF
Worley
I D
ID
Dukes
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D002478:Cells, Cultured; D004533:Egtazic Acid / Q000494:pharmacology; D016257:Fura-2; D005947:Glucose / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011189:Potassium Chloride / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D015220:Calcium Channels; D012433:Ryanodine; D002110:Caffeine; D013779:Tetrodotoxin; D004533:Egtazic Acid; D011189:Potassium Chloride; D005947:Glucose; D002118:Calcium; D016257:Fura-2