Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2011 Apr;33(8):1351-65.
doi: 10.1111/j.1460-9568.2011.07628.x. Epub 2011 Mar 14.

Molecular basis of NMDA receptor functional diversity

Pierre Paoletti  1
Affiliations
Review

Molecular basis of NMDA receptor functional diversity

Pierre Paoletti. Eur J Neurosci. 2011 Apr.

Abstract

NMDA receptors (NMDARs) form glutamate-gated ion channels widely expressed in the central nervous system and highly permeable to calcium ions. NMDARs have always attracted much attention because of their central implications in numerous physiological and pathological processes including synaptic plasticity and excitotoxicity. Ever since the discovery of NMDARs three decades ago, it has been acknowledged that native NMDARs do not form a homogeneous population of receptors but rather exist as multiple subpopulations that differ in their functional properties and, presumably, physiopathological roles. NMDARs are in fact large multi-subunit complexes arranged into heteromeric assemblies composed of four homologous subunits within a repertoire of over 10 different subunits: eight GluN1 isoforms, four GluN2 subunits (A-D) and two GluN3 subunits (A and B). This review gives an overview of our current knowledge of the molecular basis underlying NMDAR functional heterogeneity. The modular architecture and expression profile of NMDAR subunits together with the basic principles of NMDAR operation are first introduced. The influence of subunit composition on receptor functional properties is then described, with emphasis put on the impact of differential incorporation of GluN1 and GluN2 subunits (the roles of GluN3 subunits being less well understood). The final part presents recent studies revealing the central, and largely unsuspected, role of the extracellular N-terminal region in generating functional diversity of NMDARs. Indeed, the identity of this region, which is distal to the membrane and precedes the agonist-binding domains, determines key biophysical and pharmacological attributes of the various NMDAR subtypes.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

MeSH terms

Substances

LinkOut - more resources