Analysis of AMPA receptor properties during postnatal development of mouse hippocampal astrocytes. Gerald Seifert, Min Zhou, and Christian Steinh„user. Institute of Physiology, Department of Neurophysiology, University of Jena, Teichgraben 8, 07740 Jena, Germany, Experimental Neurobiology, Department of Neurosurgery, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
APStracts 4:200N, 1997.
ABSTRACT
Glial cells in the mammalian brain express various types of voltage- and ligand-gated ion channels, including glutamate receptors (GluRs) of the à- amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-subtype. 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 receptors. A fast concentration clamp technique was applied to cells acutely isolated from the CA1 stratum radiatum subregion to quantitatively analyze rapidly activating and desensitizing receptor responses. The equilibrium responses of glutamate and kainate differed between p5 and p12. While the maximum current induced by kainate was almost the same at all developmental stages, a steep rise in the maximum glutamate response was observed within the same time range. Between p5 and p12, there was an increase in the potentiation of AMPA-R currents with cyclothiazide (CTZ) while at the same time, the dissociation kinetics of CTZ became significantly slower. These changes in the pharmacological properties suggested a variation in splice variant expression. With proceeding maturation, we observed an increase in the degree of desensitization of the glutamate- and AMPA-induced receptor currents. In addition to the shift in flip/flop splicing, these findings could hint at a developmental regulation of RNA editing in the R/G site. Altogether, the present results demonstrate changes in astrocytic AMPA-R functioning early in postnatal development, while after p12 the receptor properties remained almost constant. Although the overall Ca2+ permeability did not vary during development, the prolonged receptor opening in the early postnatal period causes an enhanced Na+/Ca2+ influx into the immature astrocytes. This could influence glial proliferation and differentiation during CNS ontogenesis.

Received 18 February 1997; accepted in final form 21 August 1997.
APS Manuscript Number J137-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 28 August 1997