COINCIDENCE OF EARLY GLUCOSE-INDUCED DEPOLARIZATION WITH LOWERING OF CYTOPLASMIC CA2(+) IN MOUSE PANCREATIC BETA-CELLS
COINCIDENCE OF EARLY GLUCOSE-INDUCED DEPOLARIZATION WITH LOWERING OF CYTOPLASMIC CA2(+) IN MOUSE PANCREATIC BETA-CELLS
复制标题
DOI：
10.1113/jphysiol.1995.sp020756
复制
发表时间：
1995-06-15
影响因子：
5.5
通讯作者：
GYLFE, E
中科院分区：
文献类型：
--
作者：
CHOW, RH;LUND, PE;GYLFE, E
1.结果：1.研究了葡萄糖诱导的胰岛β细胞早期膜电位变化与胞浆内钙离子浓度（[Ca 2 +]（i））的时间关系。在3 mM葡萄糖中，平均静息膜电位和[Ca 2 +]（i）分别约为-70 mV和60 nM。将葡萄糖浓度升高至8-23 mM通常引起缓慢的去极化，其被[Ca 2 +]（i）的降低所阻碍。当缓慢去极化达到-55至-40 mV的阈值时，迅速进一步去极化至平台期，并叠加动作电位，[Ca 2 +]（i）急剧增加。4.从-70 mV的保持电位施加1.0 mV的超极化和去极化对[Ca 2 +]（i）没有可检测的影响。此外，即使在-70 mV的保持电位下，葡萄糖升高也引起[Ca 2 +]（i）的降低。阶跃去极化诱导[Ca ~（2+）]（i）瞬变，其随时间进程衰减，并通过双指数拟合。在葡萄糖升高时，较慢的组分变得更快约4倍，表明涉及ATP依赖性Ca 2+螯合或[Ca 2 +]（i）的挤出。葡萄糖刺激增加了卡巴胆碱触发的[Ca 2 +]（i）瞬变的大小并加速了其恢复，并且毒胡萝卜素（一种细胞内Ca 2 +-ATP酶抑制剂）抵消了葡萄糖诱导的[Ca 2 +]（i）的降低，表明钙转运到细胞内储存参与了葡萄糖诱导的[Ca 2 +]（i）的降低。结果支持了以下观点：在β细胞中，营养诱导的ATP升高最初导致ATP依赖性的Ca 2+从细胞质中去除，随后由于ATP敏感性K+通道的抑制而缓慢去极化。只有在去极化达到阈值后，才会发生动作电位，诱导[Ca 2 +]（i）急剧升高。
1. The temporal relationship between the early glucose-induced changes of membrane potential and cytoplasmic Ca2+ concentration ([Ca2+](i)) was studied in insulin-releasing pancreatic beta-cells.2. The mean resting membrane potential and [Ca2+](i) were about -70 mV and 60 nM, respectively, in 3 mM glucose.3. Elevating the glucose concentration to 8-23 mM typically elicited a slow depolarization, which was paralleled by a lowering of [Ca2+](i). When the slow depolarization had reached a threshold of -55 to -40 mV, there was rapid further depolarization to a plateau with superimposed action potentials, and [Ca2+](i) increased dramatically.4. Imposing hyperpolarizations and depolarizations of 1.0 mV from a holding potential of -70 mV had no detectable effect on [Ca2+](i). Furthermore, glucose elevation elicited a decrease in [Ca2+](i) even at a holding potential of -70 mV.5. Step depolarizations induced [Ca2+](i) transients, which decayed with time courses well fitted by double exponentials. The slower component became faster by a factor of about 4 upon elevation of glucose, suggesting involvement of ATP-dependent Ca2+ sequestration or extrusion of [Ca2+](i).6. Glucose stimulation increased the size and accelerated the recovery of carbachol-triggered [Ca2+](i) transients, and thapsigargin, an intracellular Ca2+-ATPase inhibitor, counteracted the glucose-induced lowering of [Ca2+](i), indicating that calcium transport into intracellular stores is involved in glucose-induced lowering of [Ca2+](i).7. The results support the notion that in beta-cells, nutrient-induced elevation of ATP leads initially to ATP-dependent removal of Ca2+ from the cytoplasm, paralleled by a slow depolarization due to inhibition of ATP-sensitive K+ channels. Only after depolarization has reached a threshold do action potentials occur, inducing a sharp elevation in [Ca2+](i).