Paranodal interactions regulate expression of sodium channel subtypes and provide a diffusion barrier for the node of Ranvier
Paranodal interactions regulate expression of sodium channel subtypes and provide a diffusion barrier for the node of Ranvier
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DOI：
10.1523/jneurosci.23-18-07001.2003
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发表时间：
2003-08-06
影响因子：
5.3
通讯作者：
Salzer, JL
中科院分区：
文献类型：
--
作者：
Rios, JC;Rubin, M;Salzer, JL
朗飞结是有髓轴突的一个独特区域，钠通道高度丰富，对于脉冲传播至关重要。在发育过程中，节点表达的通道亚型经历从 Na(v)1.2 到 Na(v)1.6 的转变。节旁神经胶质膜和轴突之间形成的特殊连接位于节点的侧面，是调节其成熟和描绘其边界的候选者。为了研究这些作用，我们对缺乏接触素相关蛋白（Caspr）（一种不可或缺的连接成分）的小鼠的节点发育进行了表征。这些小鼠的节点旁缺乏横带，这是成熟连接的标志，并且表现出中枢神经系统中轴突-节点环相互作用的逐渐破坏。 Caspr突变小鼠在中央节点表现出明显的异常；节点的组成部分沿着轴突逐渐分散，并且许多节点无法正常成熟，持续表达Na(v)1.2而不是Na(v)1.6。相比之下，PNS 节点只是稍微长一些，尽管成熟被延迟，但最终都表达 Na(v)1.6。钾通道异常聚集在旁节；随着时间的推移，这些簇在 CNS 中会丢失，但它们会在 PNS 中持续存在。这些发现表明，节旁环与轴突的相互作用促进了中枢神经系统节点处钠通道亚型的转变，并提供了横向扩散屏障，即使在没有横向带的情况下，该屏障也能维持节点处成分的高浓度和电压门控通道域的完整性。
The node of Ranvier is a distinct domain of myelinated axons that is highly enriched in sodium channels and is critical for impulse propagation. During development, the channel subtypes expressed at the node undergo a transition from Na(v)1.2 to Na(v)1.6. Specialized junctions that form between the paranodal glial membranes and axon flank the nodes and are candidates to regulate their maturation and delineate their boundaries. To investigate these roles, we characterized node development in mice deficient in contactin-associated protein (Caspr), an integral junctional component. Paranodes in these mice lack transverse bands, a hallmark of the mature junction, and exhibit progressive disruption of axon-paranodal loop interactions in the CNS. Caspr mutant mice display significant abnormalities at central nodes; components of the nodes progressively disperse along axons, and many nodes fail to mature properly, persistently expressing Na(v)1.2 rather than Na(v)1.6. In contrast, PNS nodes are only modestly longer and, although maturation is delayed, eventually all express Na(v)1.6. Potassium channels are aberrantly clustered in the paranodes; these clusters are lost over time in the CNS, whereas they persist in the PNS. These findings indicate that interactions of the paranodal loops with the axon promote the transition in sodium channel subtypes at CNS nodes and provide a lateral diffusion barrier that, even in the absence of transverse bands, maintains a high concentration of components at the node and the integrity of voltage-gated channel domains.