Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels

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 (October 2021) Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels. Pharmacological Reviews, 73 (4). pp. 298-487. ISSN 0031-6997

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URL: https://www.ncbi.nlm.nih.gov/pubmed/34753794
DOI: 10.1124/pharmrev.120.000131

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.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > small molecules > Glutamate
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > glutamate receptor
neurobiology > neuroscience
CSHL Authors:
Communities: CSHL labs > Furukawa lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: October 2021
Date Deposited: 06 Dec 2021 20:01
Last Modified: 26 Jan 2022 19:03
PMCID: PMC8626789
URI: https://repository.cshl.edu/id/eprint/40444

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