Worley J F, McIntyre M S, Spencer B, Mertz R J, Roe M W, Dukes I D
Department of Cell Physiology, Glaxo Research Institute, Research Triangle Park, North Carolina 27709.
J Biol Chem. 1994 May 20;269(20):14359-62.
Glucose stimulation of islet beta-cell insulin secretion is initiated by membrane depolarization and an elevation in intracellular free calcium concentration ([Ca2+]i) from a combination of influx through depolarization-activated Ca2+ channels and intracellular Ca2+ store release. Prevention of Ca2+ store refilling with thapsigargin produced a sustained depolarization, leading to enhanced Ca2+ influx and an elevation in [Ca2+]i in 12 mM glucose. Depletion of intracellular Ca2+ stores by external EGTA reduced [Ca2+]i and also caused a long-lasting depolarization. In single beta-cells, external EGTA activated an inward current, the voltage range and kinetic properties of which differed from those of voltage-dependent Ca2+ channels. A novel pathway thus exists in beta-cells by which depletion of endoplasmic reticulum Ca2+ stores results in the activation of an inward current that, by inducing depolarization, facilitates Ca2+ influx through voltage-gated Ca2+ channels. The physiological relevance of this pathway in the control of beta-cell function is indicated by the stimulation of insulin secretion by thapsigargin.
胰岛β细胞胰岛素分泌的葡萄糖刺激是由膜去极化以及细胞内游离钙浓度（[Ca2+]i）升高引发的，这是通过去极化激活的Ca2+通道内流和细胞内Ca2+储存释放共同作用的结果。用毒胡萝卜素阻止Ca2+储存再填充会产生持续的去极化，导致Ca2+内流增强以及在12 mM葡萄糖条件下[Ca2+]i升高。用细胞外乙二醇双四乙酸（EGTA）耗尽细胞内Ca2+储存会降低[Ca2+]i，还会引起持久的去极化。在单个β细胞中，细胞外EGTA激活了一种内向电流，其电压范围和动力学特性与电压依赖性Ca2+通道不同。因此，β细胞中存在一种新的途径，通过该途径，内质网Ca2+储存的耗尽会导致内向电流的激活，该内向电流通过诱导去极化促进Ca2+通过电压门控Ca2+通道内流。毒胡萝卜素对胰岛素分泌的刺激表明了该途径在控制β细胞功能中的生理相关性。
