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-induced Ca²⁺ fluxes in these cells were found to be attributable to the activation of AMPA receptors. Thus, these fluxes were enhanced by cyciothiazide but not by concanavalin A and were blocked completely by GYKI-53655. We simultaneously examined kainate-induced Ca²⁺ entry and Na⁺ currents in these cells under voltage-clamp conditions. Both of these parameters were blocked by Joro spider toxin (JSTx) in undifferentiated cells. However, neither JSTx nor Argiotoxin 636 effectively blocked either parameter in cells differentiated into type II astrocytes. This change in toxin sensitivity occurred slowly over a period of several days. Similar results were obtained in Ca²⁺-imaging studies. When cells were differentiated into oligodendrocytes, they showed an intermediate sensitivity to block by JSTx as assessed using imaging and voltage-clamp studies. Analysis of the expression of AMPA-receptor subunits showed an increase in the concentration of glutamate receptor-2 (GluR2) in CG-4 cells as they differentiated into type II astrocytes and oligodendrocytes. 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.