ANALYSIS OF AMPA RECEPTOR PROPERTIES DURING POSTNATAL-DEVELOPMENT OF MOUSE HIPPOCAMPAL ASTROCYTES

Glial cells in the mammalian brain express various types of voltage-an d ligand-gated ion channels, including glutamate receptors (GluRs) of the alpha-amino-3-hydroxy-5-methyl-4-is oxazolepropionic acid (AMPA)-s ubtype. In the present study we followed developmental changes in the functional properties of AMPA receptor (AMPA-R) channels expressed by astrocytes of the mouse hippocampus between postnatal days (P) 5-35 to learn more about the physiological significance of these glial recept ors. A fast concentration clamp technique was applied to cells acutely isolated from the CA1 stratum radiatum subregion to quantitatively an alyze rapidly activating and desensitizing receptor responses. The equ ilibrium responses of glutamate and kainate differed between P5 and P1 2. Although the maximum current induced by kainate was almost the same at all developmental stages, a steep rise in the maximum glutamate re sponse was observed within the same time range. Between P5 and P12 the re was an increase in the potentiation of AMPA-R currents with cycloth iazide (CTZ); at the same time, the dissociation kinetics of CTZ becam e significantly slower. These changes in the pharmacological propertie s suggested a variation in splice variant expression. With proceeding maturation, we observed an increase in the degree of desensitization o f the glutamate-and AMPA-induced receptor currents. In addition to the shift in flip/flop splicing, these findings could hint at a developme ntal regulation of RNA editing in the arginine/glycine site. Altogethe r, the present results demonstrate changes in astrocytic AMPA-R functi oning early in postnatal development, although after P12 the receptor properties remained almost constant. Although the overall Ca2+ permeab ility did not vary during development, the prolonged receptor opening in the early postnatal period causes an enhanced Na+/Ca2(+) influx int o the immature astrocytes. This could influence glial proliferation an d differentiation during CNS ontogenesis.