Upregulation of Kv 1.4 protein and gene expression after chronic spinal cord injury.
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.
Edwards
Lori
L
Division of Neurosurgery, The Toronto Western Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada M5T 2S8.
Nashmi
Raad
R
Jones
Owen
O
Backx
Peter
P
Ackerley
Cameron
C
Becker
Larry
L
Fehlings
Michael G
MG
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D001369:Axons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D002455:Cell Division / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051665:Kv1.4 Potassium Channel; D008854:Microscopy, Electron; D009413:Nerve Fibers, Myelinated / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D016900:Neurofilament Proteins / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D015854:Up-Regulation / Q000235:genetics*
D005904:Glial Fibrillary Acidic Protein; C496979:Kcna4 protein, rat; D051665:Kv1.4 Potassium Channel; D016900:Neurofilament Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; C051774:neurofilament protein H