Clustering of neuronal sodium channels requires contact with myelinating Schwann cells
Clustering of neuronal sodium channels requires contact with myelinating Schwann cells
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DOI：
10.1023/a:1007053411667
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发表时间：
1999-04-01
期刊：
影响因子：
--
通讯作者：
Salzer, JL
中科院分区：
文献类型：
--
作者：
Ching, W;Zanazzi, G;Salzer, JL
通过跳跃传导有效、快速地传导动作电位需要电压门控钠通道在郎飞叶节点处聚集。这种聚集是神经元和髓鞘神经胶质细胞之间相互作用的结果，尽管尚未确定这种神经胶质信号是接触依赖性的还是可溶的。为了研究该信号的性质，我们检查了胚胎大鼠背根神经节神经元和雪旺细胞共培养物中钠通道的聚集。在促进或阻止髓鞘形成的条件下维持的培养物用针对钠通道的α亚基和针对锚蛋白（G）（与这些通道相关的细胞骨架蛋白）的抗体进行免疫染色。与之前的体内研究一致（Vabnick 等，1996），钠通道和锚蛋白 G 在髓鞘形成开始时聚集。这些簇形成于髓鞘雪旺细胞末端附近，并似乎融合形成成熟节点。相比之下，钠通道和锚蛋白 G 不会聚集在单独生长的神经元或共培养物中，在共培养物中，在确定培养基中生长的细胞会阻止髓鞘形成。髓鞘共培养物的条件培养基也未能在单独的神经元培养物中诱导钠通道或锚蛋白 G 簇。最后，尽管背根神经节外植体的悬浮束的有髓鞘部分与培养皿的其他区域中的有髓鞘部分非常接近，但没有簇形成。这些结果表明钠通道的聚集需要与髓鞘雪旺细胞接触。
Efficient and rapid conduction of action potentials by saltatory conduction requires the clustering of voltage-gated sodium channels at nodes of Ranvier. This clustering results from interactions between neurons and myelinating glia, although it has not been established whether this glial signal is contact-dependent or soluble. To investigate the nature of this signal, we examined sodium channel clustering in co-cultures of embryonic rat dorsal root ganglion neurons and Schwann cells. Cultures maintained under conditions promoting or preventing myelination were immunostained with antibodies against the alpha subunit of the sodium channel and against ankyrin(G), a cytoskeletal protein associated with these channels. Consistent with previous in vivo studies (Vabnick et al., 1996), sodium channels and ankyrin G cluster at the onset of myelination. These clusters form adjacent to the ends of the myelinating Schwann cells and appear to fuse to form mature nodes. In contrast, sodium channels and ankyrin G do not cluster in neurons grown alone or in co-cultures where myelination is precluded by growing cells in defined media. Conditioned media from myelinating co-cultures also failed to induce sodium channel or ankyrin G clusters in cultures of neurons alone. Finally, no clusters develop in the amyelinated portions of suspended fascicles of dorsal root ganglia explants despite being in close proximity to myelinated segments in other areas of the dish. These results indicate that clustering of sodium channels requires contact with myelinating Schwann cells.