ArticleThe Journal of physiology2008
Mg2+ and memantine block of rat recombinant NMDA receptors containing chimeric NR2A/2D subunits expressed in Xenopus laevis oocytes.
Article in The Journal of physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 45 citations in OpenAlex.
- Memantine: updates from the past decade and implications for future novel therapeutic applications.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Long-Term Treatment with Fluoroethylnormemantine (FENM) Alleviated Memory Deficits, Amyloid Pathology, and Microglial Reaction in APP/PS1 Mice.ACS pharmacology & translational science · 2024Article
- A Frameshift Variant of GluN2A Identified in an Epilepsy Patient Results in NMDA Receptor Mistargeting.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- DMV extrasynaptic NMDA receptors regulate caloric intake in rats.JCI insight · 2021Article
- Potential of Medicinal Plants as Neuroprotective and Therapeutic Properties Against Amyloid-β-Related Toxicity, and Glutamate-Induced Excitotoxicity in Human Neural Cells.Current neuropharmacology · 2021Review
- Leptin modulates pancreatic β-cell membrane potential through Src kinase-mediated phosphorylation of NMDA receptors.The Journal of biological chemistry · 2020Article
- Review
- Humanin rescues cultured rat cortical neurons from NMDA-induced toxicity through the alleviation of mitochondrial dysfunction.Drug design, development and therapy · 2017Article
- Molecular bases of NMDA receptor subtype-dependent properties.The Journal of physiology · 2015Review
- Glutamate receptor pores.The Journal of physiology · 2015Review
- Ionotropic GABA and glycine receptor subunit composition in human pluripotent stem cell-derived excitatory cortical neurones.The Journal of physiology · 2014Article
- Mg2+ block properties of triheteromeric GluN1-GluN2B-GluN2D NMDA receptors on neonatal rat substantia nigra pars compacta dopaminergic neurones.The Journal of physiology · 2014Article
- The preventive effect of NR2B and NR2D-containing NMDAR antagonists on Aβ-induced LTP disruption in the dentate gyrus of rats.Metabolic brain disease · 2013Article
- TCN 201 selectively blocks GluN2A-containing NMDARs in a GluN1 co-agonist dependent but non-competitive manner.Neuropharmacology · 2012Article
- Open-channel blockade is less effective on GluN3B than GluN3A subunit-containing NMDA receptors.European journal of pharmacology · 2012Article
- Direct pharmacological monitoring of the developmental switch in NMDA receptor subunit composition using TCN 213, a GluN2A-selective, glycine-dependent antagonist.British journal of pharmacology · 2012Article
- Protection from glutamate-induced excitotoxicity by memantine.Annals of biomedical engineering · 2012Article
- A single GluN2 subunit residue controls NMDA receptor channel properties via intersubunit interaction.Nature neuroscience · 2012Article
- Negative modulation of NMDA receptor channel function by DREAM/calsenilin/KChIP3 provides neuroprotection?Frontiers in molecular neuroscience · 2012Article
- Selective inhibition of GluN2D-containing N-methyl-D-aspartate receptors prevents tissue plasminogen activator-promoted neurotoxicity both in vitro and in vivo.Molecular neurodegeneration · 2011Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
N-methyl-d-aspartate receptors (NMDARs) display differences in their sensitivity to the channel blockers Mg(2+) and memantine that are dependent on the identity of the NR2 subunit present in the receptor-channel complex. This study used two-electrode voltage-clamp recordings from Xenopus laevis oocytes expressing recombinant NMDARs to investigate the actions of Mg(2+) and memantine at the two NMDARs displaying the largest differences in sensitivity to these blockers, namely NR1/NR2A and NR1/NR2D NMDARs. In addition, NR2A/2D chimeric subunits have been employed to examine the effects of pore-forming elements and ligand-binding domains (LBD) on the potency of the block produced by each of these inhibitors. Our results show that, as previously documented, NR2D-containing NMDARs are less sensitive to voltage-dependent Mg(2+) block than their NR2A-containing counterparts. The reduced sensitivity is determined by the M1M2M3 membrane-associated regions, as replacing these regions in NR2A subunits with those found in NR2D subunits results in a approximately 10-fold reduction in Mg(2+) potency. Intriguingly, replacing the NR2A LBD with that from NR2D subunits results in a approximately 2-fold increase in Mg(2+) potency. Moreover, when responses mediated by NR1/NR2A NMDARs are evoked by the partial agonist homoquinolinate, rather than glutamate, Mg(2+) also displays an increased potency. Memantine block of glutamate-evoked currents is most potent at NR1/NR2D NMDARs, but no differences are observed in its ability to inhibit NR2A-containing or NR2A/2D chimeric NMDARs. We suggest that the potency of block of NMDARs by Mg(2+) is influenced not only by pore-forming regions but also the LBD and the resulting conformational changes that occur following agonist binding.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.