Dugandzija-Novaković S, Koszowski A G, Levinson S R, Shrager P
Department of Physiology, University of Rochester Medical Center, New York 14642.
J Neurosci. 1995 Jan;15(1 Pt 2):492-503. doi: 10.1523/JNEUROSCI.15-01-00492.1995.
Polyclonal antibodies were raised against a well conserved region of the vertebrate Na+ channel and were affinity purified for use in immunocytochemistry. Focal demyelination of rat sciatic axons was initiated by an intraneural injection of lysolecithin and Na+ channel clustering was followed at several stages of myelin removal and repair. At 1 week post-injection axons contained long, fully demyelinated regions. Na+ channel clusters appeared only at heminodes forming the borders of these zones, and at widely spaced isolated sites that may represent former nodes of Ranvier. Over the next few days proliferating Schwann cells adhered to axons and began to extend processes. Clusters of Na+ channels appeared at the edges of these structures. As the Schwann cells elongated, the clusters seemed to move with them, since they remained at edges and the distance between aggregates increased. Clusters associated with different Schwann cells ultimately approached each other and appeared to fuse. Na+ channels then coalesced further at these sites, forming new nodes of Ranvier in regions that previously were internodal. If Schwann cell proliferation were blocked by mitomycin, no new clusters of Na+ channels appeared within internodes. Under these conditions, heminodal clusters remained visible at 1 week postinjection, but by 2 weeks they were no longer detectable, suggesting that proliferating Schwann cells are required for their maintenance. Clusters at normal nodes of Ranvier remained. It is concluded that Na+ channel aggregation and mobility in demyelinated nerve fibers is controlled by adhering Schwann cells, resulting in the formation of stable new nodes of Ranvier during remyelination.
制备了针对脊椎动物钠离子通道保守区域的多克隆抗体，并对其进行亲和纯化以用于免疫细胞化学研究。通过神经内注射溶血卵磷脂引发大鼠坐骨神经轴突的局灶性脱髓鞘，并在髓鞘去除和修复的几个阶段追踪钠离子通道的聚集情况。注射后1周，轴突包含长的、完全脱髓鞘的区域。钠离子通道簇仅出现在形成这些区域边界的半结处，以及可能代表以前郎飞结的广泛间隔的孤立位点。在接下来的几天里，增殖的施万细胞粘附到轴突上并开始伸出突起。钠离子通道簇出现在这些结构的边缘。随着施万细胞伸长，这些簇似乎随着它们移动，因为它们仍留在边缘且聚集体之间的距离增加。与不同施万细胞相关的簇最终彼此靠近并似乎融合。然后钠离子通道在这些位点进一步合并，在以前是结间的区域形成新的郎飞结。如果用丝裂霉素阻断施万细胞增殖，则结间区域不会出现新的钠离子通道簇。在这些条件下，注射后1周半结簇仍然可见，但到2周时它们不再可检测到，这表明增殖的施万细胞是维持它们所必需的。正常郎飞结处的簇仍然存在。得出的结论是，脱髓鞘神经纤维中钠离子通道的聚集和移动受粘附的施万细胞控制，导致在髓鞘再生过程中形成稳定的新郎飞结。
