Voltage-dependent potassium currents in hypertrophied rat astrocytes after a cortical stab wound

Changes in the membrane properties of reactive astrocytes in gliotic cortex induced by a stab wound were studied in brain slices of 21-28-day-old rats, using the patch-clamp technique and were correlated with changes in resting extracellular K+ concentration ([K+](e)) measured in vivo using K+-selective microelectrodes. Based on K+ current expression, three types of astrocytes were identified in gliotic cortex: A1 astrocytes expressing a time- and voltage-independent K+ current component and additional inwardly rectifying K+ currents (K-IR); A2 astrocytes expressing a time- and voltage-independent K+ current component and additional delayed outwardly rectifying K+ currents (K-DR); and complex astrocytes expressing K-DR, K-IR, and A-type K+ (K-A) currents and Na+ currents (I-Na). Nestin/bromodeoxyuridine (BrdU)-negative A1 astrocytes were found further than similar to100 mum from the stab wound and showed an upregulation of K-IR currents within the first day post-injury (PI), correlating with an increased resting [K+](e). Their number declined from 62% of total astrocytes in control rats to 41% in rats at 7 days PI. Nestin/ BrdU-positive A2 astrocytes were found only within a distance of similar to100 mum from the stab wound and, in comparison to those in control rats, showed an upregulation of K-DR currents. Their number increased from 8% of the total number of astrocytes in control rats to 39% 7 days PI. Both A1 and A2 astrocytes showed hypertrophied processes and increased GFAP staining, but an examination of cell morphology revealed greater changes in the surface/volume ratio in A2 astrocytes than in A1 astrocytes. Complex astrocytes did not display a hypertophied morphology; K-IR currents in these cells were upregulated within 1 day PI, while the K-DR, K-A, and I-Na currents were increased only 6 h PI. We conclude that two electrophysiologically, immunohistochemically, and morphologically distinct types of hypertrophied astrocytes are present at the site of a stab wound, depending on the distance from the lesion, and may have different functions in ionic homeostasis and/or regeneration. (C) 2004 Wiley-Liss, Inc.