TY - JOUR
T1 - Upregulation of Kv 1.4 protein and gene expression after chronic spinal cord injury
AU - Edwards, Lori
AU - Nashmi, Raad
AU - Jones, Owen
AU - Backx, Peter
AU - Ackerley, Cameron
AU - Becker, Larry
AU - Fehlings, Michael G.
PY - 2002/2/4
Y1 - 2002/2/4
N2 - 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. © 2002 Wiley-Liss, Inc.
AB - 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. © 2002 Wiley-Liss, Inc.
KW - Axons
KW - Glia
KW - Neurotrauma
KW - Rat
KW - Voltage-gated potassium channels
U2 - 10.1002/cne.10115
DO - 10.1002/cne.10115
M3 - Article
C2 - 11793353
SN - 1096-9861
VL - 443
SP - 154
EP - 167
JO - Journal of Comparative Neurology
JF - Journal of Comparative Neurology
IS - 2
ER -