ArticleProceedings of the National Academy of Sciences of the United States of America2010
AMPA receptor desensitization mutation results in severe developmental phenotypes and early postnatal lethality.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- CaCell reports · 2025Article
- Proline substitutions in the ASIC1 β11-12 linker slow desensitization.Biophysical journal · 2024Article
- Proline substitutions in the ASIC1 β11-12 linker slow desensitization.bioRxiv : the preprint server for biology · 2024Article
- Reversible synaptic adaptations in a subpopulation of murine hippocampal neurons following early-life seizures.The Journal of clinical investigation · 2024Article
- Genetic Disruption of System xc-Mediated Glutamate Release from Astrocytes Increases Negative-Outcome Behaviors While Preserving Basic Brain Function in Rat.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- The action of Con-ikot-ikot toxin on single AMPA-type glutamate receptors.The Journal of general physiology · 2022Article
- Mutation of a conserved glutamine residue does not abolish desensitization of acid-sensing ion channel 1.The Journal of general physiology · 2021Article
- Molecular Investigation of Chicken Acid-Sensing Ion Channel 1 β11-12 Linker Isomerization and Channel Kinetics.Frontiers in cellular neuroscience · 2021Article
- Subunit-selective iGluR antagonists can potentiate heteromeric receptor responses by blocking desensitization.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- AMPA Receptor Auxiliary Subunit GSG1L Suppresses Short-Term Facilitation in Corticothalamic Synapses and Determines Seizure Susceptibility.Cell reports · 2020Article
- Measurements of the Timescale and Conformational Space of AMPA Receptor Desensitization.Biophysical journal · 2020Article
- A Central Extended Amygdala Circuit That Modulates Anxiety.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Regulation of Nociceptive Glutamatergic Signaling by Presynaptic Kv3.4 Channels in the Rat Spinal Dorsal Horn.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- A Revised View on the Role of Surface AMPAR Mobility in Tuning Synaptic Transmission: Limitations, Tools, and Alternative Views.Frontiers in synaptic neuroscience · 2018Review
- Structure and dynamics of AMPA receptor GluA2 in resting, pre-open, and desensitized states.Cell · 2014Article
- The N-terminal domain modulates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor desensitization.The Journal of biological chemistry · 2014Article
- Tethered ligands reveal glutamate receptor desensitization depends on subunit occupancy.Nature chemical biology · 2014Article
- Glutamate receptor desensitization is mediated by changes in quaternary structure of the ligand binding domain.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Cyclothiazide-induced persistent increase in respiratory-related activity in vitro.The Journal of physiology · 2012Article
- CaMKII binding to GluN2B is critical during memory consolidation.The EMBO journal · 2012Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate) recep-tors desensitize rapidly and completely in the continued presence of their endogenous ligand glutamate; however, it is not clear what role AMPA receptor desensitization plays in the brain. We generated a knock-in mouse in which a single amino acid residue, which controls desensitization, was mutated in the GluA2 (GluR2) receptor subunit (GluA2(L483Y)). This mutation was homozygous lethal. However, mice carrying a single mutated allele, GluA2(L483Y/wt), survived past birth, but displayed severe and progressive neurological deficits including seizures and, ultimately, increased mortality. The expression of the AMPA receptor subunits GluA1 and GluA2 was decreased, whereas NMDA receptor protein expression was increased in GluA2(L483Y/wt) mice. Despite this, basal synaptic transmission and plasticity in the hippocampus were largely unaffected, suggesting that neurons preferentially target receptors to synapses to normalize synaptic weight. We found no gross neuroanatomical alterations in GluA2(L483Y/wt) mice. Moreover, there was no accumulation of AMPA receptor subunits in intracellular compartments, suggesting that folding and assembly of AMPA receptors are not affected by this mutation. Interestingly, EPSC paired pulse ratios in the CA1 were enhanced without a change in synaptic release probability, demonstrating that postsynaptic receptor properties can contribute to facilitation. The dramatic phenotype observed in this study by the introduction of a single amino acid change demonstrates an essential role in vivo for AMPA receptor desensitization.
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