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GluA2-lacking AMPA receptors in hippocampal CA1 cell synapses: evidence from gene-targeted mice

The GluA2 subunit in heteromeric alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor channels restricts Ca(2+) permeability and block by polyamines, rendering linear the current-voltage relationship of these glutamate-gated cation channels. Although GluA2-lacking synaptic AMPA r...

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Detalles Bibliográficos
Autores principales: Rozov, Andrei, Sprengel, Rolf, Seeburg, Peter H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285882/
https://www.ncbi.nlm.nih.gov/pubmed/22375105
http://dx.doi.org/10.3389/fnmol.2012.00022
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author Rozov, Andrei
Sprengel, Rolf
Seeburg, Peter H.
author_facet Rozov, Andrei
Sprengel, Rolf
Seeburg, Peter H.
author_sort Rozov, Andrei
collection PubMed
description The GluA2 subunit in heteromeric alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor channels restricts Ca(2+) permeability and block by polyamines, rendering linear the current-voltage relationship of these glutamate-gated cation channels. Although GluA2-lacking synaptic AMPA receptors occur in GABA-ergic inhibitory neurons, hippocampal CA1 pyramidal cell synapses are widely held to feature only GluA2 containing AMPA receptors. A controversy has arisen from reports of GluA2-lacking AMPA receptors at hippocampal CA3-to-CA1 cell synapses and a study contesting these findings. Here we sought independent evidence for the presence of GluA2-lacking AMPA receptors in CA1 pyramidal cell synapses by probing the sensitivity of their gated cation channels in wild-type (WT) mice and gene-targeted mouse mutants to philanthotoxin, a specific blocker of GluA2-lacking AMPA receptors. The mutants either lacked GluA2 for maximal philanthotoxin sensitivity, or, for minimal sensitivity, expressed GluA1 solely in a Q/R site-edited version or not at all. Our comparative electrophysiological analyses provide incontrovertible evidence for the presence in wild-type CA1 pyramidal cell synapses of GluA2-less AMPA receptor channels. This article is part of a Special Issue entitled “Calcium permeable AMPARs in synaptic plasticity and disease.”
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spelling pubmed-32858822012-02-28 GluA2-lacking AMPA receptors in hippocampal CA1 cell synapses: evidence from gene-targeted mice Rozov, Andrei Sprengel, Rolf Seeburg, Peter H. Front Mol Neurosci Neuroscience The GluA2 subunit in heteromeric alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor channels restricts Ca(2+) permeability and block by polyamines, rendering linear the current-voltage relationship of these glutamate-gated cation channels. Although GluA2-lacking synaptic AMPA receptors occur in GABA-ergic inhibitory neurons, hippocampal CA1 pyramidal cell synapses are widely held to feature only GluA2 containing AMPA receptors. A controversy has arisen from reports of GluA2-lacking AMPA receptors at hippocampal CA3-to-CA1 cell synapses and a study contesting these findings. Here we sought independent evidence for the presence of GluA2-lacking AMPA receptors in CA1 pyramidal cell synapses by probing the sensitivity of their gated cation channels in wild-type (WT) mice and gene-targeted mouse mutants to philanthotoxin, a specific blocker of GluA2-lacking AMPA receptors. The mutants either lacked GluA2 for maximal philanthotoxin sensitivity, or, for minimal sensitivity, expressed GluA1 solely in a Q/R site-edited version or not at all. Our comparative electrophysiological analyses provide incontrovertible evidence for the presence in wild-type CA1 pyramidal cell synapses of GluA2-less AMPA receptor channels. This article is part of a Special Issue entitled “Calcium permeable AMPARs in synaptic plasticity and disease.” Frontiers Media S.A. 2012-02-24 /pmc/articles/PMC3285882/ /pubmed/22375105 http://dx.doi.org/10.3389/fnmol.2012.00022 Text en Copyright © 2012 Rozov, Sprengel and Seeburg. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
spellingShingle Neuroscience
Rozov, Andrei
Sprengel, Rolf
Seeburg, Peter H.
GluA2-lacking AMPA receptors in hippocampal CA1 cell synapses: evidence from gene-targeted mice
title GluA2-lacking AMPA receptors in hippocampal CA1 cell synapses: evidence from gene-targeted mice
title_full GluA2-lacking AMPA receptors in hippocampal CA1 cell synapses: evidence from gene-targeted mice
title_fullStr GluA2-lacking AMPA receptors in hippocampal CA1 cell synapses: evidence from gene-targeted mice
title_full_unstemmed GluA2-lacking AMPA receptors in hippocampal CA1 cell synapses: evidence from gene-targeted mice
title_short GluA2-lacking AMPA receptors in hippocampal CA1 cell synapses: evidence from gene-targeted mice
title_sort glua2-lacking ampa receptors in hippocampal ca1 cell synapses: evidence from gene-targeted mice
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285882/
https://www.ncbi.nlm.nih.gov/pubmed/22375105
http://dx.doi.org/10.3389/fnmol.2012.00022
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