DEVELOPMENTAL REGULATION OF THE TOXIN SENSITIVITY OF CA2-PERMEABLE AMPA RECEPTORS IN CORTICAL GLIA()

We examined the properties of glutamate agonist-induced Ca2+ fluxes in cultured CG-4 and O-2A progenitor cells from rat cortex. Kainate-indu ced Ca2+ fluxes in these cells were found to be attributable to the ac tivation of AMPA receptors. Thus, these fluxes were enhanced by cyclot hiazide but not by concanavalin A and were blocked completely by GYKI- 53655. We simultaneously examined kainate-induced Ca2+ entry and Na+ c urrents in these cells under voltage-clamp conditions. Both of these p arameters were blocked by Joro spider toxin (JSTx) in undifferentiated cells. However, neither JSTx nor Argiotoxin 636 effectively blocked e ither parameter in cells differentiated into type II astrocytes. This change in toxin sensitivity occurred slowly over a period of several d ays. Similar results were obtained in Ca2+-imaging studies. When cells were differentiated into oligodendrocytes, they showed an intermediat e sensitivity to block by JSTx as assessed using imaging and voltage-c lamp studies. Analysis of the expression of AMPA-receptor subunits sho wed,an increase in the concentration of glutamate receptor-2 (GluR2) i n CG-4 cells as they differentiated into type II astrocytes and oligod endrocytes. These results demonstrate that the AMPA receptors in cells of the O-2A lineage flux appreciable amounts of Ca2+ but may contain variable amounts of edited GluR2 subunits.