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

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 sugg

SUBMITTER: Borschel WF 

PROVIDER: S-EPMC3899702 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature