Electrophysiological characteristics of reactive astrocytes in experimental cortical dysplasia

Academic Article


  • Neocortical freeze lesions have been widely used to study neuronal mechanisms underlying hyperexcitability in dysplastic cortex. Comparatively little attention has been given to biophysical changes in the surrounding astrocytes that show profound morphological and biochemical alterations, often referred to as reactive gliosis. Astrocytes are thought to aid normal neuronal function by buffering extracellular K+. Compromised astrocytic K+ buffering has been proposed to contribute to neuronal dysfunction. Astrocytic K+ buffering is mediated, partially, by the activity of inwardly rectifying K+ channels (KIR) and may involve intracellular redistribution of K+ through gap-junctions. We characterized K+ channel expression and gap-junction coupling between astrocytes in freeze-lesion-induced dysplastic neocortex. Whole cell patch-clamp recordings were obtained from astrocytes in slices from postnatal day (P) 16-P24 rats that had received a freeze-lesion on P1. A marked increase in glial fibrillary acidic protein immunoreactivity was observed along the entire length of the freeze lesion. Clusters of proliferative (bromo-deoxyuridine nuclear staining, BrdU+) astrocytes were seen near the depth of the microsulcus. Astrocytes in cortical layer I surrounding the lesion were characterized by a significant reduction in KIR. BrdU-positive astrocytes near the depth of the microsulcus showed essentially no expression of KIR channels but markedly enhanced expression of delayed rectifier K+ (KDR) channels. These proliferative cells showed virtually no dye coupling, whereas astrocytes in the hyperexcitable zone adjacent to the microsulcus displayed prominent dye-coupling as well as large KIR and outward K+ currents. These findings suggest that reactive gliosis is accompanied by a loss of KIR currents and reduced gap junction coupling, which in turn suggests a compromised K+ buffering capacity.
  • Authors

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    Digital Object Identifier (doi)

    Author List

  • Bordey A; Lyons SA; Hablitz JJ; Sontheimer H
  • Start Page

  • 1719
  • End Page

  • 1731
  • Volume

  • 85
  • Issue

  • 4