Along myelinated axons, Shaker-type potassium channels (Kv1) accumulate at high density in the juxtaparanodal region, directly adjacent to the paranodal axon–glia junctions that flank the nodes of Ranvier. However, the mechanisms that control the clustering of Kv1 channels, as well as their function at this site, are still poorly understood. Here we demonstrate that axonal ADAM23 is essential for both the accumulation and stability of juxtaparanodal Kv1 complexes. The function of ADAM23 is critically dependent on its interaction with its extracellular ligands LGI2 and LGI3. Furthermore, we demonstrate that juxtaparanodal Kv1 complexes affect the refractory period, thus enabling high-frequency burst firing of action potentials. Our findings not only reveal a previously unknown molecular pathway that regulates Kv1 channel clustering, but they also demonstrate that the juxtaparanodal Kv1 channels that are concealed below the myelin sheath, play a significant role in modifying axonal physiology.

中文翻译：

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LGI3/2–ADAM23 相互作用在有髓轴突中聚集 Kv1 通道来调节不应期

沿着有髓轴突，Shaker 型钾通道 (Kv1) 在近节旁区域以高密度聚集，直接邻近朗飞节两侧的节旁轴突-神经胶质连接处。然而，人们对控制 Kv1 通道聚集的机制及其在该位点的功能仍然知之甚少。在这里，我们证明轴突 ADAM23 对于近旁节 Kv1 复合物的积累和稳定性至关重要。 ADAM23 的功能主要取决于其与其胞外配体 LGI2 和 LGI3 的相互作用。此外，我们证明近旁节 Kv1 复合体影响不应期，从而实现动作电位的高频爆发。我们的研究结果不仅揭示了以前未知的调节 Kv1 通道聚集的分子途径，而且还证明了隐藏在髓鞘下方的近节旁 Kv1 通道在改变轴突生理学方​​面发挥着重要作用。