An integrated approach to evaluate the functional effects of disease-associated NMDA receptor variants.

Ca(2+) influx Charge transfer Disease-associated variants Epilepsy Fractional Ca(2+) currents Mg(2+) block NMDA receptor dynamics Negative allosteric modulators Pore blockers Positive allosteric modulators

Journal

Neuropharmacology
ISSN: 1873-7064
Titre abrégé: Neuropharmacology
Pays: England
ID NLM: 0236217

Informations de publication

Date de publication:
01 Dec 2023
Historique:
received: 17 04 2023
revised: 30 06 2023
accepted: 31 08 2023
pubmed: 10 9 2023
medline: 10 9 2023
entrez: 9 9 2023
Statut: ppublish

Résumé

The NMDA receptor (NMDAR) is a ubiquitously expressed glutamate-gated ion channel that plays key roles in brain development and function. Not surprisingly, a variety of disease-associated variants have been identified in genes encoding NMDAR subunits. A critical first step to assess whether these variants contribute to their associated disorder is to characterize their effect on receptor function. However, the complexity of NMDAR function makes this challenging, with many variants typically altering multiple functional properties. At synapses, NMDARs encode pre- and postsynaptic activity to carry a charge transfer that alters membrane excitability and a Ca

Identifiants

pubmed: 37689262
pii: S0028-3908(23)00293-9
doi: 10.1016/j.neuropharm.2023.109703
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

109703

Informations de copyright

Copyright © 2023 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Gabrielle Moody (G)

Graduate Program in Molecular & Cellular Pharmacology, Stony Brook University, Stony Brook, NY, 11794-5230, United States.

Angela Musco (A)

Stony Brook Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, 11794-5230, United States.

Joseph Bennett (J)

Department of Neurobiology & Behavior, Stony Brook University, Stony Brook, NY, 11794-5230, United States.

Lonnie P Wollmuth (LP)

Department of Neurobiology & Behavior, Stony Brook University, Stony Brook, NY, 11794-5230, United States; Department of Biochemistry & Cell Biology, Stony Brook University, Stony Brook, NY, 11794-5230, United States; Center for Nervous System Disorders, Stony Brook University, Stony Brook, NY, 11794-5230, United States. Electronic address: lonnie.wollmuth@stonybrook.edu.

Classifications MeSH