Rasband M N, Trimmer J S, Schwarz T L, Levinson S R, Ellisman M H, Schachner M, Shrager P
Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA.
J Neurosci. 1998 Jan 1;18(1):36-47. doi: 10.1523/JNEUROSCI.18-01-00036.1998.
The K+ channel alpha-subunits Kv1.1 and Kv1.2 and the cytoplasmic beta-subunit Kvbeta2 were detected by immunofluorescence microscopy and found to be colocalized at juxtaparanodes in normal adult rat sciatic nerve. After demyelination by intraneural injection of lysolecithin, and during remyelination, the subcellular distributions of Kv1.1, Kv1.2, and Kvbeta2 were reorganized. At 6 d postinjection (dpi), axons were stripped of myelin, and K+ channels were found to be dispersed across zones that extended into both nodal and internodal regions; a few days later they were undetectable. By 10 dpi, remyelination was underway, but Kv1.1 immunoreactivity was absent at newly forming nodes of Ranvier. By 14 dpi, K+ channels were detected but were in the nodal gap between Schwann cells. By 19 dpi, most new nodes had Kv1.1, Kv1.2, and Kvbeta2, which precisely colocalized. However, this nodal distribution was transient. By 24 dpi, the majority of K+ channels was clustered within paranodal regions of remyelinated axons, leaving a gap that overlapped with Na+ channel immunoreactivity. Inhibition of Schwann cell proliferation delayed both remyelination and the development of the K+ channel distributions described. Conduction studies indicate that neither 4-aminopyridine (4-AP) nor tetraethylammonium alters normal nerve conduction. However, during remyelination, 4-AP profoundly increased both compound action potential amplitude and duration. The level of this effect matched closely the nodal presence of these voltage-dependent K+ channels. Our results suggest that K+ channels may have a significant effect on conduction during remyelination and that Schwann cells are important in K+ channel redistribution and clustering.
通过免疫荧光显微镜检测到钾离子通道α亚基Kv1.1和Kv1.2以及细胞质β亚基Kvβ2，并发现它们在正常成年大鼠坐骨神经的旁结处共定位。在通过神经内注射溶血卵磷脂进行脱髓鞘后以及再髓鞘化过程中，Kv1.1、Kv1.2和Kvβ2的亚细胞分布发生了重组。注射后6天（dpi），轴突的髓鞘被剥去，发现钾离子通道分散在延伸至结区和结间区的区域；几天后它们就检测不到了。到10 dpi时，再髓鞘化正在进行，但在新形成的郎飞结处没有Kv1.1免疫反应性。到14 dpi时，检测到钾离子通道，但位于施万细胞之间的结间隙中。到19 dpi时，大多数新结处有Kv1.1、Kv1.2和Kvβ2，它们精确共定位。然而，这种结区分布是短暂的。到24 dpi时，大多数钾离子通道聚集在再髓鞘化轴突的旁结区域内，留下一个与钠离子通道免疫反应性重叠的间隙。抑制施万细胞增殖会延迟再髓鞘化以及上述钾离子通道分布的发育。传导研究表明，4-氨基吡啶（4-AP）和四乙铵都不会改变正常神经传导。然而，在再髓鞘化过程中，4-AP显著增加了复合动作电位的幅度和持续时间。这种效应的程度与这些电压依赖性钾离子通道在结处的存在密切匹配。我们的结果表明，钾离子通道可能在再髓鞘化过程中对传导有显著影响，并且施万细胞在钾离子通道的重新分布和聚集方面很重要。
