Relative abundance of subunit mRNAs determines gating and Ca2+ permeability of AMPA receptors in principal neurons and interneurons in rat CNS

Abstract

Recording of glutamate-activated currents in membrane patches was combined with RT-PCR-mediated AMPA receptor (AMPAR) subunit mRNA analysis in single identified cells of rat brain slices. Analysis of AMPARs in principal neurons and interneurons of hippocampus and neocortex and in auditory relay neurons and Bergmann glial cells indicates that the GluR-B subunit in its flip version determines formation of receptors with relatively slow gating, whereas the GluR-D subunit promotes assembly of more rapidly gated receptors. The relation between Ca2+ permeability of AMPAR channels and the relative GluR-B mRNA abundance is consistent with the dominance of this subunit in determining the Ca2+ permeability of native receptors. The results suggest that differential expression of GluR-B and GluR-D subunit genes, as well as splicing and editing of their mRNAs, account for the differences in gating and Ca2+ permeability of native AMPAR channels.

Multiple behavioral anomalies in GluR2 mutant mice exhibiting enhanced LTP

“…Since in the mutant mice Ca 2 + permeability may be increased in all neurons that would normally express GluR2 (mostly pyramidal and granule cells [19]), the absence of this protein may lead to non-specific synaptic strengthening throughout the brain. Our present behavioral findings therefore are significant in that they suggest the involvement of multiple brain areas and not only the hippocampus, the target of a previous study.…”

Molecular mechanisms controlling synaptic recruitment of GluA4 subunit-containing AMPA-receptors critical for functional maturation of CA1 glutamatergic synapses

“…Homomeric GluA4 AMPA receptors and in particular, the GluA4 'flop' splice variants show faster kinetics as compared to other types of AMPARs (Mosbacher et al, 1994;Geiger et al, 1995;Zhu, 2009), which may affect the amount of depolarization at postsynaptic neurons in response to receptor activation. The decay time of AMPA EPSCs increased during development in both WT and GluA4-/-mice (p<0.001); however, no significant differences in the kinetics of the AMPA EPSCs were detected between the genotypes at any stage of development (P4-P5: WT 4.2±0.6 ms, GluA4-/-4.6±0.4 ms; P6-P8: WT 5.6±0.7 ms, GluA4-/-5.7±0.8 ms; P14-P15: WT 10.5±0.8 ms, GluA4-/-9.6±0.8 ms; P16-P34: WT 9.3±0.9 ms, GluA4-/-10.2±0.5 ms).…”

Coding interaural time differences at low best frequencies in the barn owl

“…The brevity of these currents depends not only on the time course of release but also on the specific properties of the postsynaptic AMPA receptors. AMPA receptors in time coding auditory neurons have fast kinetics and rapid desensitization rates, leading to very short EPSCs [30][31][32]88]. Although brief EPSCs underlie the rapid synaptic potential changes seen in time coding neurons, the intrinsic electrical properties of these neurons also shape the synaptic response as well as the temporal firing pattern.…”