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          Institute: MPI für medizinische Forschung     Collection: Abteilung Molekulare Neurobiologie     Display Documents

ID: 23256.0, MPI für medizinische Forschung / Abteilung Molekulare Neurobiologie
Selective activation of NR2A-containing NMDA receptors in CA1 pyramidal cell synapses by spontaneously released glutamate
Translation of Title:Selective activation of NR2A-containing NMDA receptors in CA1 pyramidal cell synapses by spontaneously released glutamate
Authors:Steigerwald, Frank; Schulz, Torsten W.; Schenker, Leslie T.; Kennedy, Mary B.; Seeburg, Peter H.; Köhr, Georg
Date of Publication (YYYY-MM-DD):2000-06-15
Title of Journal:Journal of Neuroscience
Journal Abbrev.:J. Neurosci.
Issue / Number:12
Start Page:4573
End Page:4581
Review Status:Peer-review
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:NMDA receptors interact via the extended intracellular C-terminal domain of the NR2 subunits with constituents of the postsynaptic density for purposes of retention, clustering, and functional regulation at central excitatory synapses. To examine the role of the C-terminal domain of NR2A in the synaptic localization and function of NR2A-containing NMDA receptors in hippocampal Schaffer collateral-CA1 pyramidal cell synapses, we analyzed mice which express NR2A only in its C-terminally truncated form. In CA1 cell somata, the levels, activation, and deactivation kinetics of extrasynaptic NMDA receptor channels were comparable in wild-type and mutant NR2ADelta C/Delta C mice. At CA1 cell synapses, however, the truncated receptors were less concentrated than their full-length counterparts, as indicated by immunodetection in cultured neurons, synaptosomes, and postsynaptic densities. In the mutant, the NMDA component of evoked EPSCs was reduced in a developmentally progressing manner and was even more reduced in miniature EPSCs (mEPSCs) elicited by spontaneous glutamate release. Moreover, pharmacologically isolated NMDA currents evoked by synaptic stimulation had longer latencies and displayed slower rise and decay times, even in the presence of an NR2B-specific antagonist. These data strongly suggest that the C-terminal domain of NR2A subunits is important for the precise synaptic arrangement of NMDA receptors.
Free Keywords:immunocytochemistry; Western blotting; patch clamp; hippocampal culture and slice; mice expressing C-terminally truncated NR2A subunits; nucleated patches; evoked EPSCs; miniature currents; NR2B-specific antagonists (CP-101,606)
External Publication Status:published
Document Type:Article
Communicated by:Wulf Kaiser
Affiliations:MPI für medizinische Forschung/Abteilung Biophysik/
MPI für medizinische Forschung/Abteilung Molekulare Neurobiologie/
Identifiers:URI:http://www.jneurosci.org/cgi/content/full/20/12/45... [Full text]
URI:http://www.jneurosci.org/cgi/content/abstract/20/1... [Abstract]
URI:http://www.jneurosci.org/cgi/reprint/20/12/4573?ma... [Fulltext PDF]
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