Influence of GluN2 subunit identity on NMDA receptor function
Open accessAbstract
N-methyl-d-aspartate receptors (NMDARs) are ligand-gated ion channels ('ionotropic' receptors) activated by the major excitatory neurotransmitter, l-glutamate. While the term 'the NMDAR' is often used it obscures the fact that this class of receptor contains within it members whose properties are as different as they are similar. This heterogeneity was evident from early electrophysiological, pharmacological and biochemical assessments of the functional properties of NMDARs and while the molecular basis of this heterogeneity has taken many years to elucidate, it indicated from the outset that the diversity of NMDAR phenotypes could allow this receptor family to subserve a variety of functions in the mammalian central nervous system. In this review we highlight some recent studies that have identified structural elements within GluN2 subunits that contribute to the heterogeneous biophysical properties of NMDARs, consider why some recently described novel pharmacological tools may permit better identification of native NMDAR subtypes, examine the evidence that NMDAR subtypes differentially contribute to the induction of long-term potentiation and long-term depression and discuss how through the use of chimeric proteins additional insights have been obtained that account for NMDAR subtype-dependency of physiological and pathophysiological signalling. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'.
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NMDARs are permeant to Ca2+, which mediates many consequences of NMDAR activity, including synaptic modification, learning and memory, activity-dependent development, and neuroprotective/homeostatic signaling.
“They are permeant to Ca 2+ , which mediates many of the consequences of NMDAR activity, including synaptic modification, learning and memory, activity-dependent development, and neuroprotective/homeostatic signaling [6][7][8] .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · cites this paper as [7]
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“A long-standing debate in the field concerns the differential contribution of GluN2A- and GluN2B-containing NMDARs to excitotoxic neuronal death (Wyllie et al., 2013).”
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- Authors
- Wyllie, D. J. A., Livesey, M. R., & Hardingham, G. E.
- Affiliations
- University of Edinburgh (GB)
- Corresponding author
- Wyllie, D.J.A.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 74
- Pages
- 4-17
- ISSN
- 0028-3908 (ISSN-L)
- PMC
- PMC3778433
- OpenAlex
- W2108909652
- Cited by
- 260
- References
- 161
- Citations by year
- 2026: 6 · 2025: 27 · 2024: 21 · 2023: 16 · 2022: 29 · 2021: 24 · 2020: 20 · 2019: 23 · 2018: 26 · 2017: 18 · 2016: 18 · 2015: 16 · 2014: 10 · 2013: 5
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Neuropharmacology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- The Wellcome Trust
- The Medical Research Council
- The Biotechnology and Biological Science Research Council
- The European Union
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- NMDA receptor, GluN2 subunits, receptor heterogeneity, ionotropic glutamate receptors, receptor subtypes, long-term potentiation, long-term depression, synaptic plasticity, fusion protein, receptor pharmacology, glutamate signalling
- MeSH terms
- Animals, Models, Molecular, Neuronal Plasticity, Receptors, N-Methyl-D-Aspartate, Long-Term Potentiation, Excitatory Amino Acid Antagonists, Protein Subunits, Protein Multimerization
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