Glucose-induced mixed [Ca2+]c oscillations in mouse β-cells are controlled by the membrane potential and the SERCA3 Ca2+-ATPase of the endoplasmic reticulum
Glucose-induced mixed [Ca2+]c oscillations in mouse β-cells are controlled by the membrane potential and the SERCA3 Ca2+-ATPase of the endoplasmic reticulum
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DOI：
10.1152/ajpcell.00400.2005
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发表时间：
2006-06-01
影响因子：
5.5
通讯作者：
Gilon, P
中科院分区：
文献类型：
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作者：
Beauvois, MC;Merezak, C;Gilon, P
葡萄糖的刺激浓度诱导两种模式的细胞质Ca2+浓度（[Ca2+](c)）振荡在小鼠胰岛：简单或混合。在混合模式中，快速振荡叠加在慢振荡上。在本研究中，我们研究了膜电位在混合模式中的作用以及这种模式对胰岛素释放的影响。同时测量单个胰岛的[Ca2+](c)和胰岛素释放表明，混合[Ca2+](c)振荡触发胰岛素分泌的同步振荡。同时记录胰岛内单个β细胞的膜电位和整个胰岛内[Ca2+](c)的膜电位表明，混合模式是由复合破裂（即膜电位振荡簇被长时间沉默间隔分开）引起的，这在大多数胰岛β细胞中是同步的。在混合振荡期间，每一次缓慢的[Ca2+](c)增加都是由于快速振荡的渐进求和。数字图像分析证实了一个小岛子区域之间的良好同步性。相比之下，sarco（endo）质网Ca2+- atp酶异构体3 （SERCA3）敲除小鼠的胰岛在葡萄糖反应中没有表现出典型的混合[Ca2+](c)振荡。这是由于缺乏快速振荡的渐进式累积和自发电活动的改变，即缺乏化合物破裂和膜电位振荡，其特征是比在SERCA3(+/+) β细胞中观察到的频率更低，但退极化期更大。我们得出结论，葡萄糖诱导的混合[Ca2+](c)振荡是由胰岛所有β细胞的化合物破裂引起的。SERCA3的破坏可消除混合[Ca2+](c)振荡并增强β细胞去极化。后一种观察结果表明，内质网参与葡萄糖刺激时β细胞膜电位的控制。
Stimulatory concentrations of glucose induce two patterns of cytosolic Ca2+ concentration ([Ca2+](c)) oscillations in mouse islets: simple or mixed. In the mixed pattern, rapid oscillations are superimposed on slow ones. In the present study, we examined the role of the membrane potential in the mixed pattern and the impact of this pattern on insulin release. Simultaneous measurement of [Ca2+](c) and insulin release from single islets revealed that mixed [Ca2+](c) oscillations triggered synchronous oscillations of insulin secretion. Simultaneous recordings of membrane potential in a single beta-cell within an islet and of [Ca2+](c) in the whole islet demonstrated that the mixed pattern resulted from compound bursting (i.e., clusters of membrane potential oscillations separated by prolonged silent intervals) that was synchronized in most beta-cells of the islet. Each slow [Ca2+](c) increase during mixed oscillations was due to a progressive summation of rapid oscillations. Digital image analysis confirmed the good synchrony between sub-regions of an islet. By contrast, islets from sarco(endo) plasmic reticulum Ca2+-ATPase isoform 3 (SERCA3)-knockout mice did not display typical mixed [Ca2+](c) oscillations in response to glucose. This results from a lack of progressive summation of rapid oscillations and from altered spontaneous electrical activity, i.e., lack of compound bursting, and membrane potential oscillations characterized by lower-frequency but larger-depolarization phases than observed in SERCA3(+/+) beta-cells. We conclude that glucose-induced mixed [Ca2+](c) oscillations result from compound bursting in all beta-cells of the islet. Disruption of SERCA3 abolishes mixed [Ca2+](c) oscillations and augments beta-cell depolarization. This latter observation indicates that the endoplasmic reticulum participates in the control of the beta-cell membrane potential during glucose stimulation.