Dependence of nodal sodium channel clustering on paranodal axoglial contact in the developing CNS
Dependence of nodal sodium channel clustering on paranodal axoglial contact in the developing CNS
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DOI：
10.1523/jneurosci.19-17-07516.1999
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发表时间：
1999-09-01
影响因子：
5.3
通讯作者：
Shrager, P
中科院分区：
文献类型：
--
作者：
Rasband, MN;Peles, E;Shrager, P
分析了发育中的大鼠视神经Ranvier节点上Na+通道的聚集，以确定其定位的机制，包括体内可能需要胶质接触。髓鞘相关糖蛋白和轴胶质连接成分Caspr蛋白的免疫荧光标记表明，早在出生后第7天就出现了少突胶质细胞，并形成了副结结构（P7）。然而，第一个Na+通道簇直到P9才被发现。这些大多是广泛的，所有被排除在旁神经区域的轴交接触。从P12到P22，检测到的Na+通道簇数量迅速增加。在同一时期，传导速度急剧增加，Na+通道簇变得更加聚焦。为了进一步检验少突胶质细胞接触是否直接影响Na+通道分布，我们检测了低髓鞘小鼠Shiverer的Ranvier淋巴结。该突变体具有少突胶质细胞包裹的轴突，但缺乏致密的髓鞘和正常的轴胶质连接。发育过程中，Shiverer小鼠的Na+通道簇数量减少，位置异常。Caspr的亚细胞定位被破坏，神经传导特性仍然不成熟。这些结果表明，在体内，Na+通道在节点上的聚集不仅取决于少突胶质细胞的存在，还取决于旁结处特定的轴胶质接触。在大鼠中，锚蛋白-3/G，一种与Na+通道聚集有关的细胞骨架蛋白，在Na+通道免疫反应之前被检测到，但在非淋巴结分布中扩展到偏执狂。在Shiverer中，锚蛋白-3/G标记异常，表明其定位也依赖于轴角接触。
Na+ channel clustering at nodes of Ranvier in the developing rat optic nerve was analyzed to determine mechanisms of localization, including the possible requirement for glial contact in vivo. Immunofluorescence labeling for myelin-associated glycoprotein and for the protein Caspr, a component of axoglial junctions, indicated that oligodendrocytes were present, and paranodal structures formed, as early as postnatal day 7 (P7). However, the first Na+ channel clusters were not seen until P9. Most of these were broad, and all were excluded from paranodal regions of axoglial contact. The number of detected Na+ channel clusters increased rapidly from P12 to P22. During this same period, conduction velocity increased sharply, and Na+ channel clusters became much more focal. To test further whether oligodendrocyte contact directly influences Na+ channel distributions, nodes of Ranvier in the hypomyelinating mouse Shiverer were examined. This mutant has oligodendrocyte-ensheathed axons but lacks compact myelin and normal axoglial junctions. During development Na+ channel clusters in Shiverer mice were reduced in numbers and were in aberrant locations. The subcellular location of Caspr was disrupted, and nerve conduction properties remained immature. These results indicate that in vivo, Na+ channel clustering at nodes depends not only on the presence of oligodendrocytes but also on specific axoglial contact at paranodal junctions. In rats, ankyrin-3/G, a cytoskeletal protein implicated in Na+ channel clustering, was detected before Na+ channel immunoreactivity but extended into paranodes in non-nodal distributions. In Shiverer, ankyrin-3/G labeling was abnormal, suggesting that its localization also depends on axoglial contact.