Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels
Open accessAbstract
Many physiologic effects of l-glutamate, the major excitatory neurotransmitter in the mammalian central nervous system, are mediated via signaling by ionotropic glutamate receptors (iGluRs). These ligand-gated ion channels are critical to brain function and are centrally implicated in numerous psychiatric and neurologic disorders. There are different classes of iGluRs with a variety of receptor subtypes in each class that play distinct roles in neuronal functions. The diversity in iGluR subtypes, with their unique functional properties and physiologic roles, has motivated a large number of studies. Our understanding of receptor subtypes has advanced considerably since the first iGluR subunit gene was cloned in 1989, and the research focus has expanded to encompass facets of biology that have been recently discovered and to exploit experimental paradigms made possible by technological advances. Here, we review insights from more than 3 decades of iGluR studies with an emphasis on the progress that has occurred in the past decade. We cover structure, function, pharmacology, roles in neurophysiology, and therapeutic implications for all classes of receptors assembled from the subunits encoded by the 18 ionotropic glutamate receptor genes. SIGNIFICANCE STATEMENT: Glutamate receptors play important roles in virtually all aspects of brain function and are either involved in mediating some clinical features of neurological disease or represent a therapeutic target for treatment. Therefore, understanding the structure, function, and pharmacology of this class of receptors will advance our understanding of many aspects of brain function at molecular, cellular, and system levels and provide new opportunities to treat patients.
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NMDARs are heterotetrameric ligand-gated ionotropic receptors.
“NMDARs are heterotetrameric ligand-gated ionotropic receptors”
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Li, Y., Guo, Y., Bröer, A., Dai, L., Brӧer, S., & Yan, R. (2024) · Nature Communications · doi:10.1038/s41467-024-47468-1 · Cited by 12 · see citing works
Glutamate receptor 4 as a fluid biomarker for the diagnosis of psychiatric disorders
Gómez de San José, N., Goossens, J., Al Shweiki, M. R., Halbgebauer, S., Oeckl, P., Steinacker, P., Danzer, K. M., Graf, H., Schönfeldt-Lecuona, C., Belbin, O., et al. (2022) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2022.10.010 · Cited by 9 · see citing works
- Authors
- Hansen, K. B., Wollmuth, L. P., Bowie, D., Furukawa, H., Menniti, F. S., Sobolevsky, A. I., Swanson, G. T., Swanger, S. A., Greger, I. H., Nakagawa, T., McBain, C. J., Jayaraman, V., Low, C.-M., Dell’Acqua, M. L., Diamond, J. S., Camp, C. R., Perszyk, R. E., Yuan, H., & Traynelis, S. F.
- Affiliations
- Northwestern University (US)
- Corresponding author
- Traynelis, Stephen F.
- ORCID
- Hansen, Kasper B.
- Wollmuth, Lonnie P.
- Bowie, Derek
- Furukawa, Hiro
- Menniti, Frank S.
- Sobolevsky, Alexander I.
- Swanson, Geoffrey T.
- Swanger, Sharon A.
- Greger, Ingo H.
- Nakagawa, Terunaga
- McBain, Chris J.
- Jayaraman, Vasanthi
- Low, Chian-Ming
- Dell’Acqua, Mark L.
- Diamond, Jeffrey S.
- Camp, Chad R.
- Perszyk, Riley E.
- Yuan, Hongjie
- Traynelis, Stephen F.
- Venue
- Pharmacological Reviews
- Publisher
- Elsevier BV
- Published
- 2021-10
- Volume
- 73
- Issue
- 4
- Pages
- 1469-1658
- ISSN
- 0031-6997 (ISSN-L)
- PMC
- PMC8626789
- OpenAlex
- W3214054678
- Cited by
- 686
- References
- 2,576
- Citations by year
- 2026: 123 · 2025: 198 · 2024: 160 · 2023: 115 · 2022: 81 · 2021: 9
- FWCI
- 13.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Pharmacological Reviews (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Funders
- National Institutes of Health (5f31ns113530-02)
- Biotechnology and Biological Sciences Research Council (BB/N002113/1)
- National Institute of Mental Health (R56MH123474, R21MH127404, R01MH085926, R01MH123474)
- National Cancer Institute (R01CA206573)
- National Institute of General Medical Sciences (P20GM103546, R35GM122528)
- National Institute of Neurological Disorders and Stroke (F31‐NS113530, R01NS105804, R56NS040701, R01NS083660, R01NS040701, R01NS088479, R01NS111745, RF1NS113632, R01NS105502, R01NS107253, R35NS111619, R37NS083660, R01NS116055, R01NS097536)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD082373)
- 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, glutamate, receptor subtypes, receptor structure, receptor pharmacology, excitatory neurotransmission, neurophysiology, neurological disorders, mental illness, therapeutic target
- MeSH terms
- Animals, Central Nervous System, Humans, Receptors, Glutamate, Neurotransmitter Agents, Glutamic Acid, Receptors, Ionotropic Glutamate
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