Glutamate Receptor Ion Channels: Structure, Regulation, and Function

Pharmacological Reviews, Journal Year: 2010, Volume and Issue: 62(3), P. 405 - 496

Published: Aug. 17, 2010

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

Language: Английский

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Cellular and Synaptic Mechanisms of Anti-NMDA Receptor Encephalitis

Journal of Neuroscience, Journal Year: 2010, Volume and Issue: 30(17), P. 5866 - 5875

Published: April 28, 2010

We recently described a severe, potentially lethal, but treatment-responsive encephalitis that associates with autoantibodies to the NMDA receptor (NMDAR) and results in behavioral symptoms similar those obtained models of genetic or pharmacologic attenuation NMDAR function. Here, we demonstrate patients' antibodies cause selective reversible decrease surface density synaptic localization correlates antibody titers. The mechanism this is antibody-mediated capping internalization NMDARs, as Fab fragments prepared from did not density, subsequent cross-linking anti-Fab recapitulated caused by intact patient antibodies. Moreover, whole-cell patch-clamp recordings miniature EPSCs cultured rat hippocampal neurons showed specifically decreased NMDAR-mediated currents, without affecting AMPA receptor-mediated currents. In contrast these profound effects on alter expression other glutamate receptors proteins, number synapses, dendritic spines, complexity, cell survival. addition, was dramatically reduced hippocampus female Lewis rats infused antibodies, observed autopsied patients. These studies establish cellular mechanisms through which patients anti-NMDAR specific, titer-dependent, loss NMDARs. subtype eliminates function, resulting learning, memory, deficits encephalitis.

Language: Английский

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How the Timing and Quality of Early Experiences Influence the Development of Brain Architecture

Child Development, Journal Year: 2010, Volume and Issue: 81(1), P. 28 - 40

Published: Jan. 1, 2010

Early life events can exert a powerful influence on both the pattern of brain architecture and behavioral development. In this study conceptual framework is provided for considering how structure early experience gets “under skin.” The begins with description genetic that lays foundation development, then proceeds to ways interacts modifies structures functions developing brain. Much attention focused sensitive periods, although it made clear later also plays an important role in maintaining elaborating wiring diagram, which critical establishing solid footing development beyond years.

Language: Английский

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TrkB signalling pathways in LTP and learning

Nature reviews. Neuroscience, Journal Year: 2009, Volume and Issue: 10(12), P. 850 - 860

Published: Nov. 20, 2009

Language: Английский

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AMPARs and Synaptic Plasticity: The Last 25 Years

Neuron, Journal Year: 2013, Volume and Issue: 80(3), P. 704 - 717

Published: Oct. 1, 2013

Language: Английский

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Antibodies to the GABAB receptor in limbic encephalitis with seizures: case series and characterisation of the antigen

The Lancet Neurology, Journal Year: 2009, Volume and Issue: 9(1), P. 67 - 76

Published: Dec. 4, 2009

Language: Английский

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Actin in action: the interplay between the actin cytoskeleton and synaptic efficacy

Nature reviews. Neuroscience, Journal Year: 2008, Volume and Issue: 9(5), P. 344 - 356

Published: April 18, 2008

Language: Английский

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AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location

Annals of Neurology, Journal Year: 2009, Volume and Issue: 65(4), P. 424 - 434

Published: March 19, 2009

To report the clinical and immunological features of a novel autoantigen related to limbic encephalitis (LE) effect patients' antibodies on neuronal cultures.We conducted analyses 10 patients with LE. Immunoprecipitation mass spectrometry were used identify antigens. Human embryonic kidney 293 cells expressing antigens in immunocytochemistry enzyme-linked immunoabsorption assay. The cultures live rat hippocampal neurons was determined confocal microscopy.Median age 60 (38-87) years; 9 women. Seven had tumors lung, breast, or thymus. Nine responded immunotherapy oncological therapy, but neurological relapses, without tumor recurrence, frequent influenced long-term outcome. One untreated patient died All against cell surface that by immunoprecipitation found be glutamate receptor 1 (GluR1) GluR2 subunits alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPAR). GluR1/2 reacted all sera cerebrospinal fluid, providing diagnostic test for disorder. Application significantly decreased number GluR2-containing AMPAR clusters at synapses smaller decrease overall cluster density; these effects reversed after antibody removal.Antibodies associate LE is often paraneoplastic, treatment responsive, has tendency relapse. Our findings support an antibody-mediated pathogenesis which alter synaptic localization AMPARs.

Language: Английский

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A Brief History of Long-Term Potentiation

Neuron, Journal Year: 2017, Volume and Issue: 93(2), P. 281 - 290

Published: Jan. 1, 2017

Language: Английский

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The AMPA Receptor Code of Synaptic Plasticity

Neuron, Journal Year: 2018, Volume and Issue: 100(2), P. 314 - 329

Published: Oct. 1, 2018

Language: Английский

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