Cited by 686Neuroscience and Neuropharmacology ResearchNicotinic Acetylcholine Receptors StudyReceptor Mechanisms and Signaling

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Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels

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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.·2021·Pharmacological Reviews

DOI 10.1124/pharmrev.120.000131PMC PMC8626789

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Abstract

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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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)
DOI: 10.1124/pharmrev.120.000131
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
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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Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels

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