Cited by 3,568Neuroscience and Neuropharmacology ResearchNicotinic Acetylcholine Receptors StudyReceptor Mechanisms and Signaling

Glutamate Receptor Ion Channels: Structure, Regulation, and Function

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Traynelis, Stephen F., Wollmuth, Lonnie P., McBain, Chris J., Menniti, Frank S., Vance, Katie M., Ogden, Kevin K., Hansen, Kasper B., Yuan, Hongjie +2 more·2010·Pharmacological Reviews

Abstract

The mammalian ionotropic glutamate receptor family encodes 18 gene products that coassemble to form ligand-gated ion channels containing an agonist recognition site, a transmembrane ion permeation pathway, and gating elements that couple agonist-induced conformational changes to the opening or closing of the permeation pore. Glutamate receptors mediate fast excitatory synaptic transmission in the central nervous system and are localized on neuronal and non-neuronal cells. These receptors regulate a broad spectrum of processes in the brain, spinal cord, retina, and peripheral nervous system. Glutamate receptors are postulated to play important roles in numerous neurological diseases and have attracted intense scrutiny. The description of glutamate receptor structure, including its transmembrane elements, reveals a complex assembly of multiple semiautonomous extracellular domains linked to a pore-forming element with striking resemblance to an inverted potassium channel. In this review we discuss International Union of Basic and Clinical Pharmacology glutamate receptor nomenclature, structure, assembly, accessory subunits, interacting proteins, gene expression and translation, post-translational modifications, agonist and antagonist pharmacology, allosteric modulation, mechanisms of gating and permeation, roles in normal physiological function, as well as the potential therapeutic use of pharmacological agents acting at glutamate receptors.

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Crossref · 10.1124/pr.109.002451

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  • NMDARs are heterotetrameric ligand-gated ionotropic receptors.

    “NMDARs are heterotetrameric ligand-gated ionotropic receptors”

    From Mechanisms of ketamine and its metabolites as antidepressants (2022) · cites this paper as Traynelis et al., 2010

  • The NMDAR ion channel is heteromeric, composed of two obligatory GluN1 subunits and two GluN2 or GluN3 subunits.

    “The NMDAR ion channel is heteromeric, composed of two obligatory GluN1 subunits and two GluN2 or GluN3 subunits.”
  • Expression of GluN1 is necessary for the formation of a functional NMDAR channel in the plasma membrane.

    “Expression of GluN1 is necessary for the formation of a functional NMDAR channel in the plasma membrane.19”
  • The proposed role of glutamate as a signal molecule in ctenophores is supported by an unprecedented diversity of ionotropic glutamate receptors far exceeding the number of genes encoding iGluRs in other basal metazoans.

    “The proposed role of glutamate as a signal molecule in ctenophores is supported by an unprecedented diversity of ionotropic glutamate receptors(iGluRs;ExtendedDataFig.7a,bandSupplementaryTable27)far exceeding the number of genes encoding iGluRs in other basal metazoans 28 .”

    From The ctenophore genome and the evolutionary origins of neural systems (2014) · cites this paper as [28]

    The Introduction and Nomenclature and Subunit Organization and Quaternary Structure passages describe ionotropic glutamate receptors generally, but do not discuss ctenophores or compare receptor-gene counts across basal metazoans. Searches for ctenophores, comb jellies, and comparative receptor repertoires found no passage addressing the attributed claim; the copy is truncated. (LLM, conf=0.70)

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  • Throughout the central nervous system, the vast majority of fast synaptic neurotransmission arises via AMPARs.

    “Throughout the central nervous system, the vast majority of fast synaptic neurotransmission arises via AMPARs (1133).”

    From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [1133]

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Authors
Traynelis, S. F., Wollmuth, L. P., McBain, C. J., Menniti, F. S., Vance, K. M., Ogden, K. K., Hansen, K. B., Yuan, H., Myers, S. J., & Dingledine, R.
Affiliations
Emory University (US)
Venue
Pharmacological Reviews
Publisher
Elsevier BV
Published
2010-09
Volume
62
Issue
3
Pages
405-496
ISSN
0031-6997 (ISSN-L)
OpenAlex
W2037852973
Cited by
3,568
References
1,399
Citations by year
2026: 151 · 2025: 181 · 2024: 216 · 2023: 201 · 2022: 247 · 2021: 279 · 2020: 269 · 2019: 272 · 2018: 235 · 2017: 268 · 2016: 242 · 2015: 221 · 2014: 257 · 2013: 221 · 2012: 162
FWCI
15.66
Type
journal article
Language
en
Update notices
erratum (2014-10-01)
Open access
Locations
  • Pharmacological Reviews (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Michael J. Fox Foundation for Parkinson's Research
  • Lundbeckfonden
  • H. Lundbeck A/S
  • National Institutes of Health (NS036654)
  • National Institute of Mental Health (MH066892, R01MH066892)
  • National Institute on Drug Abuse (T32-DA01504006, T32DA015040)
  • National Eye Institute (R01EY016979, EY01697905)
  • National Institute of General Medical Sciences (GM008602, T32GM008602)
  • National Institute of Neurological Disorders and Stroke (R37NS036654, NS036604, NS068464, R01NS065371, NS065371, R01NS036654, NS036654, R01NS068464, R01NS036604)
  • National Institute of Environmental Health Sciences (T32ES012870)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
ionotropic glutamate receptors, ligand-gated ion channels, receptor structure, receptor assembly, auxiliary subunits, receptor regulation, post-translational modification, allosteric modulation, gating mechanism, ion permeation, excitatory synaptic transmission, receptor nomenclature, neurological disorders, therapeutic agents
MeSH terms
Humans, Ion Channels, Synaptic Transmission, Terminology as Topic, Protein Processing, Post-Translational, Gene Expression, Receptors, Glutamate, Protein Subunits

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