Role of voltage-dependent ionic currents in coupling glucose stimulation to insulin secretion in canine pancreatic islet B-cells.
Role of voltage-dependent ionic currents in coupling glucose stimulation to insulin secretion in canine pancreatic islet B-cells.
复制标题
电压依赖性离子电流在犬胰岛 B 细胞中葡萄糖刺激与胰岛素分泌耦合中的作用。
DOI：
10.1007/bf01994357
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Misler,S
中科院分区：
文献类型：
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作者：
Pressel,DM;Misler,S
犬胰岛B细胞中葡萄糖诱导的电活动与啮齿动物胰岛中的不同，尽管两者都显示Ca2+依赖性胰岛素分泌。啮齿动物胰岛B细胞经历钙离子依赖性动作电位的规律爆发，而犬胰岛B细胞产生孤立的钠离子依赖性动作电位，其通常让位于平台去极化。在这里，我们提出的证据来调和的物种差异的电活动与相似的Ca2+依赖的分泌。(i)在犬B细胞中，增加葡萄糖浓度会导致膜去极化，并增加Na+依赖性动作电位的频率，直至达到背景膜电位（± 40 mV），此时Na+电流失活。(ii)存在电压依赖性Ca2+电流，其在动作电位的电压偏移（−50至+20 mV）范围内被激活，并在平台去极化（−40至−25 mV）范围内缓慢激活（持续数秒）。因此，它们可用于促进去极化的两个阶段。(iii)河豚毒素（TTX）减少一半的早期短暂阶段的葡萄糖估计的胰岛素分泌，但不是随后延长的平台期。分泌的瞬时相通常在时间上与初始高频动作电位活动的时期很好地对应。后者的结果表明，在犬B细胞电压依赖性Na+和Ca 2+电流介导双相葡萄糖诱导的胰岛素分泌。Na+依赖性动作电位的早期序列通过瞬时激活Ca 2+通道并允许脉动式Ca 2+进入，可促进胰岛素分泌的早期瞬时相。随后的持续平台去极化，通过允许持续的Ca2+进入，可以允许稳定的胰岛素释放。
Glucose-induced electrical activity in canine pancreatic islet B cells is distinct from that in rodent islets, though both display Ca2+-dependent insulin secretion. Rodent islet B cells undergo regular bursts of Ca2+-dependent action potentials, while canine islet B cells generate isolated Na+-dependent action potentials which often give way to a plateau depolarization. Here we present evidence to reconcile the species difference in electrical activity with the similarity of Ca2+dependence of secretion. (i) In canine B cells increasing glucose concentrations produce membrane depolarization and increasing frequency of Nao-dependent action potentials until a background membrane potential (∼-40mV) is reached where Na+currents are inactivated. (ii) Voltage-dependent Ca2+currents are present which are activated over the voltage excursion of the action potential (−50 to +20 mV) and inactivate slowly, (over seconds) in the range of the plateau depolarization (−40 to −25 mV). Hence, they are available to contribute to both phases of depolarization. (iii) Tetrodotoxin (TTX) reduces by half an early transient phase of glucosestimulated insulin secretion but not a subsequent prolonged plateau phase. The transient phase of secretion often corresponds well in time to the period of initial high frequency action potential activity. These latter results suggest that in canine B cells voltagedependent Na+and Ca2+currents mediate biphasic glucose-induced insulin secretion. The early train of Na+-dependent action potentials, by transiently activating Ca2+channels and allowing pulsatile Ca2+entry, may promote an early transient phase of insulin secretion. The subsequent sustained plateau depolarization, by allowing sustained Ca2+entry, may permit steady insulin release.