AMPA glutamate receptor-mediated calcium signaling is transiently enhanced during development of oligodendrocytes
AMPA glutamate receptor-mediated calcium signaling is transiently enhanced during development of oligodendrocytes
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DOI：
10.1046/j.1471-4159.2002.00866.x
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发表时间：
2002-04-01
影响因子：
4.7
通讯作者：
Pleasure, D
中科院分区：
文献类型：
--
作者：
Itoh, T;Beesley, J;Pleasure, D
少突胶质细胞谱系的细胞在发育过程中表达Ca 2+可渗透的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸盐偏好谷氨酸受体（AMPA-GluR）。AMPA-GluR的长期激活导致Ca 2+超载，导致兴奋性中毒死亡。先前的研究表明，少突胶质祖细胞和未成熟的少突胶质细胞对兴奋性毒性敏感，而成熟的少突胶质细胞具有抗性。一个尚未解决的问题是为什么AMPA-GluR的Ca 2+渗透性随着少突胶质细胞的发育而变化如此显著，尽管编辑的GluR 2（阻断Ca 2+进入的AMPA-GluR亚基）的表达水平相对恒定。为了解决这个问题，我们进行了钙离子成像，分子和电生理分析，使用纯化的培养物的大鼠少突胶质细胞系。我们表明，短暂的上调表达的GluR 3和GluR 4亚基的少突胶质细胞的祖细胞和未成熟的少突胶质细胞的结果在这些细胞的组装，但不是由少突胶质细胞前祖细胞或成熟的少突胶质细胞，AMPA-GluR的人口缺乏GluR 2。这种阶段特异性的上调编辑GluR 2自由，因此Ca 2+渗透，AMPA-GluR解释了选择性易感性兴奋毒性的细胞在这些阶段的少突胶质细胞分化，并可能是重要的，这些细胞在跨突触Ca 2+信号从海马神经元，这发生在海马体内。
Cells of the oligodendroglial lineage express Ca2+-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate-preferring glutamate receptors (AMPA-GluR) during development. Prolonged activation of their AMPA-GluR causes Ca2+ overload, resulting in excitotoxic death. Prior studies have shown that oligodendroglial progenitors and immature oligodendrocytes are susceptible to excitotoxicity, whereas mature oligodendrocytes are resistant. An unresolved issue has been why Ca2+-permeability of AMPA-GluR varies so markedly with oligodendroglial development, although the level of expression of edited GluR2, an AMPA-GluR subunit which blocks Ca2+ entry, is relatively constant. To address this question, we performed Ca2+ imaging, molecular and electrophysiological analyses using purified cultures of the rat oligodendroglial lineage. We demonstrate that transient up-regulation of expression of GluR3 and GluR4 subunits in oligodendroglial progenitors and immature oligodendrocytes results in the assembly by these cells, but not by oligodendroglial pre-progenitors or mature oligodendrocytes, of a population of AMPA-GluR which lack GluR2. This stage-specific up-regulation of edited GluR2-free, and hence Ca2+-permeable, AMPA-GluR explains the selective susceptibility to excitotoxicity of cells at these stages of oligodendroglial differentiation, and is likely to be important to these cells in the trans-synaptic Ca2+-signaling from glutamatergic neurons, which occurs in hippocampus in vivo.