The GluN3-containing NMDA receptors

N-methyl-D-aspartate receptors (NMDARs) are heterotetrameric ion channels that play crucial roles in brain function. Among all the NMDAR subtypes, GluN1-N3 receptors exhibit unique agonist binding and gating properties. Unlike “conventional” GluN1-N2 receptors, which require both glycine and glutama...

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Bibliographic Details
Main Authors: Kunlong Xiong, Shulei Lou, Zuoyu Lian, Yunlin Wu, Zengwei Kou
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Channels
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Online Access:https://www.tandfonline.com/doi/10.1080/19336950.2025.2490308
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Summary:N-methyl-D-aspartate receptors (NMDARs) are heterotetrameric ion channels that play crucial roles in brain function. Among all the NMDAR subtypes, GluN1-N3 receptors exhibit unique agonist binding and gating properties. Unlike “conventional” GluN1-N2 receptors, which require both glycine and glutamate for activation, GluN1-N3 receptors are activated solely by glycine. Furthermore, GluN1-N3 receptors display faster desensitization, reduced Ca2+ permeability, and lower sensitivity to Mg2+ blockage compared to GluN1-N2 receptors. Due to these characteristics, GluN1-N3 receptors are thought to play critical roles in eliminating redundant synapses and pruning spines in early stages of brain development. Recent studies have advanced pharmacological tools for specifically targeting GluN1-N3 receptors and provided direct evidence of these glycine-activated excitatory receptors in native brain tissue. The structural basis of GluN1-N3 receptors has also been elucidated through cryo-EM and artificial intelligence. These findings highlight that GluN1-N3 receptors are not only involved in essential brain functions but also present potential targets for drug development.
ISSN:1933-6950
1933-6969