Electrophysiological characteristics of reactive astrocytes in experimental cortical dysplasia

Neocortical freeze lesions have been widely used to study neuronal mechanis ms underlying hyperexcitability in dysplastic cortex. Comparatively little attention has been given to biophysical changes in the surrounding astrocyt es that show profound morphological and biochemical alterations, often refe rred 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+ buf fering is mediated, partially, by the activity of inwardly rectifying K+ ch annels (K-IR) and may involve intracellular redistribution of K+ through ga p-junctions. We characterized K+ channel expression and gap-junction coupli ng between astrocytes in freeze-lesion-induced dysplastic neocortex. Whole cell patch-clamp recordings were obtained from astrocytes in slices from po stnatal day (P) 16-P24 rats that had received a freeze-lesion on P1. A mark ed increase in glial fibrillary acidic protein immunoreactivity was observe d along the entire length of the freeze lesion. Clusters of proliferative ( bromo-deoxyuridine nuclear staining, BrdU+) astrocytes were seen near the d epth of the microsulcus. Astrocytes in cortical layer I surrounding the les ion were characterized by a significant reduction in K-IR. BrdU-positive as trocytes near the depth of the microsulcus showed essentially no expression of K-IR channels but markedly enhanced expression of delayed rectifier K(K-DR) 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 K-IR and outward K+ curr ents. These findings suggest that reactive gliosis is accompanied by a loss of K-IR currents and reduced gap junction coupling, which in turn suggests a compromised K+ buffering capacity.