NMDA receptor activation requires remodelling of intersubunit contacts within ligand-binding heterodimers

William F. Borschel, Swetha E. Murthy, Eileen M. Kasperek and Gabriela K. Popescu ()
Additional contact information
William F. Borschel: University of Buffalo
Swetha E. Murthy: University of Buffalo
Eileen M. Kasperek: University of Buffalo
Gabriela K. Popescu: University of Buffalo

Nature Communications, 2011, vol. 2, issue 1, 1-6

Abstract: Abstract Two classes of glutamate-activated channels mediate excitation at central synapses: N-methyl-D-aspartic acid (NMDA) receptors and non-NMDA receptors. Despite substantial structural homology, each class generates signals with characteristic kinetics and mediates distinct synaptic functions. In non-NMDA receptors, the strength of intersubunit contacts within ligand-binding domains is inversely correlated with functional desensitization. Here we test how the strength of these contacts affects NMDA receptor activation by combining mutagenesis and single-channel current analyses. We show that receptors with covalently linked dimers had significantly lower activity due to high barriers to opening and unstable open states but had intact desensitization. On the basis of these observations, we suggest that in NMDA receptors rearrangements at the heterodimer interface represent an early and integral step of the opening sequence but are not required for desensitization. These results demonstrate distinct functional roles in the activation of NMDA and non-NMDA glutamate-gated channels for largely conserved intersubunit contacts.

Date: 2011
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms1512 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1512

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms1512

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().