Store-operated calcium entry is essential for glial calcium signalling in CNS white matter.

Store-operated calcium entry is essential for glial calcium signalling in CNS white matter.
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DOI:
10.1007/s00429-017-1380-8
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发表时间:
2017-09
影响因子:
3.1
通讯作者:
Butt AM
Butt AM
中科院分区:
医学3区
文献类型:
--
作者:
Papanikolaou M;Lewis A;Butt AM

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“钙信号传导”是神经胶质细胞对多种细胞外刺激的普遍反应。神经胶质细胞钙信号传导的主要机制是通过内质网(ER)的细胞内储存释放钙。ER钙库的补充依赖于钙库操作的钙进入(SOCE)。然而,尽管钙信号在神经胶质细胞中的重要性,很少有人知道他们的机制SOCE。在这里,我们研究了小鼠视神经胶质细胞的SOCE,视神经是一种典型的CNS白色物质束,包括成束的有髓轴突和支持它们的少突胶质细胞和星形胶质细胞。使用定量RT-PCR,我们确定Orai 1通道,Stim 1和Stim 2,和瞬时受体电位M3通道(TRPM 3)的主要渠道SOCE在视神经,和他们的表达在星形胶质细胞和少突胶质细胞的免疫标记的视神经切片和培养证明。SOCE的功能重要性通过对分离的完整视神经和视神经培养物的Fluo-4钙成像来证明。细胞外钙([Ca 2 +]o)的去除导致胶质细胞胞浆钙([Ca 2 +]i)的显著耗竭,其在通过SOCE恢复[Ca 2 +]o后迅速恢复。2-氨基乙氧基二苯基硼烷(2APB)显着降低SOCE和严重衰减ATP介导的钙信号。结果提供的证据表明,奥赖/Stim和TRPM 3是“钙工具包”的重要组成部分,支持SOCE和白色胶质细胞中钙信号的可持续性。
‘Calcium signalling’ is the ubiquitous response of glial cells to multiple extracellular stimuli. The primary mechanism of glial calcium signalling is by release of calcium from intracellular stores of the endoplasmic reticulum (ER). Replenishment of ER Ca2+ stores relies on store-operated calcium entry (SOCE). However, despite the importance of calcium signalling in glial cells, little is known about their mechanisms of SOCE. Here, we investigated SOCE in glia of the mouse optic nerve, a typical CNS white matter tract that comprises bundles of myelinated axons and the oligodendrocytes and astrocytes that support them. Using quantitative RT-PCR, we identified Orai1 channels, both Stim1 and Stim2, and the transient receptor potential M3 channel (TRPM3) as the primary channels for SOCE in the optic nerve, and their expression in both astrocytes and oligodendrocytes was demonstrated by immunolabelling of optic nerve sections and cultures. The functional importance of SOCE was demonstrated by fluo-4 calcium imaging on isolated intact optic nerves and optic nerve cultures. Removal of extracellular calcium ([Ca2+]o) resulted in a marked depletion of glial cytosolic calcium ([Ca2+]i), which recovered rapidly on restoration of [Ca2+]o via SOCE. 2-aminoethoxydiphenylborane (2APB) significantly decreased SOCE and severely attenuated ATP-mediated calcium signalling. The results provide evidence that Orai/Stim and TRPM3 are important components of the ‘calcium toolkit’ that underpins SOCE and the sustainability of calcium signalling in white matter glia.
少突胶质细胞中的任务1通道:缺血介导的破坏中的作用。
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发表时间: 2013-07
影响因子: 6.1
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