Glutamate Receptor Ion Channels: Structure, Regulation, and Function
Stephen F. Traynelis,Lonnie P. Wollmuth,Chris J. McBain,Frank S. Menniti,Katie M. Vance,Kevin K. Ogden,Kasper B. Hansen,Hongjie Yuan,Scott J. Myers,Raymond Dingledine +9 more
TLDR
This review discusses 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.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.read more
Citations
More filters
Journal ArticleDOI
NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease
TL;DR: The effects of subunit composition on NMDAR properties, synaptic plasticity and cellular mechanisms implicated in neuropsychiatric disorders are reviewed and could provide new therapeutic strategies against dysfunctions of glutamatergic transmission.
Journal ArticleDOI
Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals
James J. Lee,Robbee Wedow,Aysu Okbay,Edward Kong,Omeed Maghzian,Meghan Zacher,Tuan Anh Nguyen-Viet,Peter Bowers,Julia Sidorenko,Julia Sidorenko,Richard Karlsson Linnér,Richard Karlsson Linnér,Mark Alan Fontana,Mark Alan Fontana,Tushar Kundu,Chanwook Lee,Hui Li,Ruoxi Li,Rebecca Royer,Pascal Timshel,Pascal Timshel,Raymond K. Walters,Raymond K. Walters,Emily A. Willoughby,Loic Yengo,Maris Alver,Yanchun Bao,David W. Clark,Felix R. Day,Nicholas A. Furlotte,Peter K. Joshi,Peter K. Joshi,Kathryn E. Kemper,Aaron Kleinman,Claudia Langenberg,Reedik Mägi,Joey W. Trampush,Shefali S. Verma,Yang Wu,Max Lam,Jing Hua Zhao,Zhili Zheng,Zhili Zheng,Jason D. Boardman,Harry Campbell,Jeremy Freese,Kathleen Mullan Harris,Caroline Hayward,Pamela Herd,Pamela Herd,Meena Kumari,Todd Lencz,Todd Lencz,Jian'an Luan,Anil K. Malhotra,Anil K. Malhotra,Andres Metspalu,Lili Milani,Ken K. Ong,John R. B. Perry,David J. Porteous,Marylyn D. Ritchie,Melissa C. Smart,Blair H. Smith,Joyce Y. Tung,Nicholas J. Wareham,James F. Wilson,Jonathan P. Beauchamp,Dalton Conley,Tõnu Esko,Steven F. Lehrer,Steven F. Lehrer,Steven F. Lehrer,Patrik K. E. Magnusson,Sven Oskarsson,Tune H. Pers,Tune H. Pers,Matthew R. Robinson,Matthew R. Robinson,Kevin Thom,Chelsea Watson,Christopher F. Chabris,Michelle N. Meyer,David Laibson,Jian Yang,Magnus Johannesson,Philipp Koellinger,Philipp Koellinger,Patrick Turley,Patrick Turley,Peter M. Visscher,Daniel J. Benjamin,Daniel J. Benjamin,David Cesarini,David Cesarini +94 more
TL;DR: A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11–13% of the variance ineducational attainment and 7–10% ofthe variance in cognitive performance, which substantially increases the utility ofpolygenic scores as tools in research.
Journal ArticleDOI
Gliotransmitters Travel in Time and Space
Alfonso Araque,Giorgio Carmignoto,Philip G. Haydon,Stéphane H. R. Oliet,Richard Robitaille,Andrea Volterra +5 more
TL;DR: It is proposed that astrocytes mainly signal through high-affinity slowly desensitizing receptors to modulate neurons and perform integration in spatiotemporal domains complementary to those of neurons.
Journal ArticleDOI
AMPARs and Synaptic Plasticity: The Last 25 Years
TL;DR: The progress over the last two and a half decades is reviewed, the future challenges in the field are discussed and a large number of proteins have been identified that regulate this complex process.
Journal ArticleDOI
Alpha and gamma oscillations characterize feedback and feedforward processing in monkey visual cortex.
Timo van Kerkoerle,Matthew W. Self,Bruno Dagnino,Marie-Alice Gariel-Mathis,Jasper Poort,Chris van der Togt,Pieter R. Roelfsema,Pieter R. Roelfsema +7 more
TL;DR: It is concluded that high- and low-frequency oscillations provide markers of feedforward and feedback processing, respectively.
References
More filters
Journal ArticleDOI
The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R).
Ronald C. Kessler,Patricia A. Berglund,Olga Demler,Robert Jin,Doreen S. Koretz,Kathleen R. Merikangas,A. John Rush,Ellen E. Walters,Philip S. Wang +8 more
TL;DR: Notably, major depressive disorder is a common disorder, widely distributed in the population, and usually associated with substantial symptom severity and role impairment, and while the recent increase in treatment is encouraging, inadequate treatment is a serious concern.
Journal ArticleDOI
The Structure of the Potassium Channel: Molecular Basis of K+ Conduction and Selectivity
Declan A. Doyle,João H.Morais Cabral,Richard A. Pfuetzner,Anling Kuo,Jacqueline M. Gulbis,Steven L. Cohen,Brian T. Chait,Roderick MacKinnon +7 more
TL;DR: The architecture of the pore establishes the physical principles underlying selective K+ conduction, which promotes ion conduction by exploiting electrostatic repulsive forces to overcome attractive forces between K+ ions and the selectivity filter.
Journal Article
The glutamate receptor ion channels
TL;DR: The cloning of cDNAs encoding glutamate receptor subunits, which occurred mainly between 1989 and 1992, stimulated the development of ionotropic glutamate receptors in the brain.
Journal ArticleDOI
Magnesium gates glutamate-activated channels in mouse central neurones
TL;DR: The voltage dependence of the NMDA receptor-linked conductance appears to be a consequence of the voltage dependenceof the Mg2+ block and its interpretation does not require the implication of an intramembrane voltage-dependent ‘gate’.
Journal ArticleDOI
Pathobiology of ischaemic stroke: an integrated view
TL;DR: This article provides a framework that can be used to generate testable hypotheses and treatment strategies that are linked to the appearance of specific pathophysiological events within the ischaemic brain.