Characterization of Kv 1.4 potassium ion channel expression after spinal cord injury and its association with oligodendrocyte precursor cell proliferation.

摘要

Introduction. The improvement of axonal conduction and neurological function after treatment with K+ channel blockers in animal models and patients with spinal cord injury (SCI) has lead to the investigation of voltage-gated K+ channel expression in the spinal cord and how this expression may change after injury. This thesis characterizes changes in expression of the K+ channel subunit Kv 1.4 after SCI and the potential association between these changes and posttraumatic proliferation of oligodendrocyte progenitor cells (OPC).; Methods. Localization of Kv 1.4 protein expression in the spinal cord was conducted using immunohistochemisty with specific cell markers for neurons/axons, astrocytes, oligodendrocytes, OPC and microglia. Changes in Kv 1.4 protein and mRNA expression after SCI were investigated using semi-quantitative Western blotting, immunogold electron microscopy and in situ hybridization. The association between Kv 1.4 expression and OPC proliferation after SCI was examined by using Bromodeoxyuridine (BrdU) to identify proliferating cells and labeling for Kv 1.4 protein.; Results. Kv 1.4 localized to oligodendrocytes, astrocytes and OPC but not microglia or myelinated axons in normal and injured spinal cord white matter. The expression of Kv 1.4 was upregulated in oligodendroglial cells at 6 weeks but not 1 week after SCI. Although there was an increase after SCI in the number of glial cells expressing Kv 1.4, the number of OPC expressing Kv 1.4 was not significantly increased. Kv 1.4 expression was not temporally or spatially associated with BrdU positive cells after SCI and the expression of other K+ channel subunits potentially involved in OPC proliferation (Kv 1.5 and 1.6) was not increased 6 weeks after SCI.; Conclusions. Kv 1.4 is expressed in spinal cord glial cells and is upregulated in oligodendroglial cells after chronic SCI. This upregulation in Kv 1.4 is not associated with changes in OPC proliferation, suggesting other potential roles for this glial K+ channel subunit after SCI.