ArticleNature neuroscience2014
Mechanical coupling maintains the fidelity of NMDA receptor-mediated currents.
Article in Nature neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
73 citing papers in PubMed, 93 citations in OpenAlex.
- Subconductance states in NMDA receptor variants are CaResearch square · 2026Article
- GluA4 AMPA receptor gating mechanisms and modulation by auxiliary proteins.Nature structural & molecular biology · 2025Article
- Regulation of NMDAR activation efficiency by environmental factors and subunit composition.The Journal of general physiology · 2025Article
- Electrically silent mutants unravel the mechanism of binding-gating coupling in Cys-loop receptors.Science advances · 2024Article
- Mechanisms of Action Underlying Conductance-Modifying Positive Allosteric Modulators of the NMDA Receptor.Molecular pharmacology · 2024Article
- Article
- Disease-associated nonsense and frame-shift variants resulting in the truncation of the GluN2A or GluN2B C-terminal domain decrease NMDAR surface expression and reduce potentiating effects of neurosteroids.Cellular and molecular life sciences : CMLS · 2024Article
- An integrated approach to evaluate the functional effects of disease-associated NMDA receptor variants.Neuropharmacology · 2023Article
- Two gates mediate NMDA receptor activity and are under subunit-specific regulation.Nature communications · 2023Article
- Complex functional phenotypes of NMDA receptor disease variants.Molecular psychiatry · 2022Article
- Structural basis of AMPA receptor inhibition by trans-4-butylcyclohexane carboxylic acid.British journal of pharmacology · 2022Article
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- The diverse and complex modes of action of anti-NMDA receptor autoantibodies.Neuropharmacology · 2021Review
- Structural biology and thermodynamics of GluD receptors.Neuropharmacology · 2021Review
- Palmitoylation Controls NMDA Receptor Function and Steroid Sensitivity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- NMDA Receptors Require Multiple Pre-opening Gating Steps for Efficient Synaptic Activity.Neuron · 2021Article
- Cross-subunit interactions that stabilize open states mediate gating in NMDA receptors.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- From bedside-to-bench: What disease-associated variants are teaching us about the NMDA receptor.The Journal of physiology · 2021Review
- Potential Roles of Redox Dysregulation in the Development of Schizophrenia.Biological psychiatry · 2020Review
- Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The fidelity of integration of pre- and postsynaptic activity by NMDA receptors (NMDARs) requires a match between agonist binding and ion channel opening. To address how agonist binding is transduced into pore opening in NMDARs, we manipulated the coupling between the ligand-binding domain (LBD) and the ion channel by inserting residues in a linker between them. We found that a single residue insertion markedly attenuated the ability of NMDARs to convert a glutamate transient into a functional response. This was largely a result of a decreased likelihood of the channel opening and remaining open. Computational and thermodynamic analyses suggest that insertions prevent the agonist-bound LBD from effectively pulling on pore lining elements, thereby destabilizing pore opening. Furthermore, this pulling energy was more prominent in the GluN2 subunit. We conclude that an efficient NMDAR-mediated synaptic response relies on a mechanical coupling between the LBD and the ion channel.
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Registered trials
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.