ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Asynchronous movements prior to pore opening in NMDA receptors.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 55 citations in OpenAlex.
- Article
- Regulation of NMDAR activation efficiency by environmental factors and subunit composition.The Journal of general physiology · 2025Article
- Clinical phenotype and functional influence of GRIN2A variants in epilepsy-aphasia syndrome.Epilepsia open · 2024Article
- Structural insights into NMDA receptor pharmacology.Biochemical Society transactions · 2023Review
- 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
- Effects of ethanol on GluN1/GluN2A and GluN1/GluN2B NMDA receptor-ion channel gating kinetics.Alcoholism, clinical and experimental research · 2022Article
- Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.Pharmacological reviews · 2021Review
- 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
- Biased modulators of NMDA receptors control channel opening and ion selectivity.Nature chemical biology · 2020Article
- Prying open a glutamate receptor gate.The Journal of general physiology · 2019Article
- The NMDA receptor intracellular C-terminal domains reciprocally interact with allosteric modulators.Biochemical pharmacology · 2019Article
- A conserved glycine harboring disease-associated mutations permits NMDA receptor slow deactivation and high CaNature communications · 2018Article
- A structurally derived model of subunit-dependent NMDA receptor function.The Journal of physiology · 2018Article
- Structure, function, and allosteric modulation of NMDA receptors.The Journal of general physiology · 2018Review
- Kinetic models for activation and modulation of NMDA receptor subtypes.Current opinion in physiology · 2018Article
- Structural modeling for the open state of an NMDA receptor.Journal of structural biology · 2017Article
- Divergent roles of a peripheral transmembrane segment in AMPA and NMDA receptors.The Journal of general physiology · 2017Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Glutamate-gated ion channels embedded within the neuronal membrane are the primary mediators of fast excitatory synaptic transmission in the CNS. The ion channel of these glutamate receptors contains a pore-lining transmembrane M3 helix surrounded by peripheral M1 and M4 helices. In the NMDA receptor subtype, opening of the ion channel pore, mediated by displacement of the M3 helices away from the central pore axis, occurs in a highly concerted fashion, but the associated temporal movements of the peripheral helices are unknown. To address the gating dynamics of the peripheral helices, we constrained the relative movements of the linkers that connect these helices to the ligand-binding domain using engineered cross-links, either within (intra-GluN1 or GluN2A) or between subunits. Constraining the peripheral linkers in any manner dramatically curtailed channel opening, highlighting the requirement for rearrangements of these peripheral structural elements for efficient gating to occur. However, the magnitude of this gating effect depended on the specific subunit being constrained, with the most dramatic effects occurring when the constraint was between subunits. Based on kinetic and thermodynamic analysis, our results suggest an asynchrony in the displacement of the peripheral linkers during the conformational and energetic changes leading to pore opening. Initially there are large-scale rearrangements occurring between the four subunits. Subsequently, rearrangements occur within individual subunits, mainly GluN2A, leading up to or in concert with pore opening. Thus, the conformational changes induced by agonist binding in NMDA receptors converge asynchronously to permit pore opening.
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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.