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