VOLTAGE-DEPENDENT INTRACELLULAR CALCIUM RELEASE FROM MOUSE ISLETS STIMULATED BY GLUCOSE

Glucose-activated beta-cell insulin secretion depends upon elevation o f intracellular calcium concentration, [Ca2+]i, which is thought to ar ise from Ca2+ influx through voltage-dependent calcium channels. Using fura-2-loaded mouse islets, we demonstrate, in fact, that the major c omponent of the glucose-activated [Ca2+]i rise represents voltage-depe ndent intracellular Ca2+ release. Furthermore, the Ca2+ release pool p ossesses a novel pharmacology in that it is caffeine-sensitive but rya nodine-insensitive. In the absence of external Ca2+, glucose still cau sed intracellular Ca2+ release, an effect blockable by tetrodotoxin. H owever, depolarization of the islet with KCl in low Ca2+-containing so lutions induced intracellular Ca2+ release, which was resistant to tet rodotoxin. We conclude that glucose release of intracellular Ca2+ is d ependent upon depolarization alone, possibly through increasing inosit ol 1,4,5-trisphosphate production.