Edwards Lori, Nashmi Raad, Jones Owen, Backx Peter, Ackerley Cameron, Becker Larry, Fehlings Michael G
Division of Neurosurgery, The Toronto Western Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada M5T 2S8.
J Comp Neurol. 2002 Feb 4;443(2):154-67. doi: 10.1002/cne.10115.
After spinal cord injury (SCI), white matter tracts are characterized by demyelination and increased sensitivity to the K(+) channel blocker 4-aminopyridine (4-AP). These effects appear to contribute to neurological impairment after SCI, although the molecular changes in K(+) channel subunit expression remain poorly understood. We examined changes in gene expression of the 4-AP-sensitive voltage-gated K(+) channel Kv 1.4 after chronic SCI in the rat. Quantitative immunoblotting showed that Kv 1.4 protein was significantly increased at 6 weeks, but not at 1 week, after SCI in spinal cord white matter. Kv 1.4 was localized to astrocytes, oligodendrocytes, and oligodendrocyte progenitor cells but not to axons in both the normal and the injured spinal cord white matter. Because glial cells proliferate after SCI, we used immunogold electron microscopy to quantify Kv 1.4 protein in individual glial cells and found a sixfold increase of Kv 1.4 in cells of the oligodendrocyte lineage after chronic injury. Finally, quantitative in situ hybridization showed that Kv 1.4 mRNA was significantly upregulated in spinal cord white matter, but not gray matter, after SCI. In summary, we show that Kv 1.4 is expressed in glial cells and not in axons in the rat spinal cord white matter and that its expression is markedly increased in cells of the oligodendrocyte lineage after chronic SCI. Given that K(+) channels play a role in glial cell proliferation, cells exhibiting changes in Kv 1.4 expression may represent proliferating oligodendroglia in the chronically injured spinal cord.
脊髓损伤（SCI）后，白质束的特征是脱髓鞘以及对钾（K+）通道阻滞剂4-氨基吡啶（4-AP）的敏感性增加。这些效应似乎导致了SCI后的神经功能障碍，尽管钾通道亚基表达的分子变化仍知之甚少。我们研究了大鼠慢性SCI后4-AP敏感的电压门控钾通道Kv 1.4的基因表达变化。定量免疫印迹显示，脊髓损伤后6周脊髓白质中Kv 1.4蛋白显著增加，但1周时未增加。在正常和损伤的脊髓白质中，Kv 1.4定位于星形胶质细胞、少突胶质细胞和少突胶质前体细胞，但不定位于轴突。由于SCI后胶质细胞会增殖，我们使用免疫金电子显微镜对单个胶质细胞中的Kv 1.4蛋白进行定量，发现慢性损伤后少突胶质细胞系细胞中的Kv 1.4增加了六倍。最后，定量原位杂交显示，SCI后脊髓白质中Kv 1.4 mRNA显著上调，但灰质中未上调。总之，我们表明Kv 1.4在大鼠脊髓白质的胶质细胞中表达，而不在轴突中表达，并且在慢性SCI后其在少突胶质细胞系细胞中的表达明显增加。鉴于钾通道在胶质细胞增殖中起作用，Kv 1.4表达发生变化的细胞可能代表慢性损伤脊髓中增殖的少突胶质细胞。
