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PMID: 11466429 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Subunit interactions and AMPA receptor desensitization.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 21 ·No. 15 ·2001-08-01 ·Pages 5574-86

Robert A, Irizarry SN, Hughes TE, Howe JR

Abstract

Most AMPA-type glutamate receptors (GluRs) exhibit rapid and virtually complete desensitization when activated by glutamate, and at some central synapses it is largely desensitization that determines the decay of EPSCs. However, the mechanisms underlying the conformation change that results in desensitization are not fully understood. AMPA receptor subunits that contain a single amino acid substitution have been shown to form homomeric channels that show markedly reduced desensitization. We show here that the coexpression of wild-type GluR1 with one such mutant, GluR1(L497Y), results in heteromeric channels that show desensitization behavior that is intermediate between wild-type and mutant homomers. The relative amplitudes of the multiple exponential components present in the decay of glutamate-evoked currents depended on the relative abundance of wild-type and mutant subunits and were described by the combinatorial distribution of the two types of subunits into tetrameric, but not pentameric, assemblies. Our results are consistent with recent structural data suggesting that AMPA receptors are tetrameric assemblies composed of two dimers.

MeSH Terms
Amino Acid Substitution Animals Cell Line Cells, Cultured Dimerization Excitatory Postsynaptic Potentials/drug effects,physiology Gene Expression Glutamic Acid/metabolism,pharmacology Kidney/cytology,metabolism Models, Neurological Mutagenesis, Site-Directed Neurons/metabolism Patch-Clamp Techniques Phenotype Protein Binding Protein Subunits Rats Rats, Sprague-Dawley Reaction Time/drug effects,physiology Receptors, AMPA/genetics,metabolism Transfection
Chemicals
Protein Subunits Receptors, AMPA Glutamic Acid glutamate receptor ionotropic, AMPA 1
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Robert A
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520-8066, USA.
Irizarry S N
Hughes T E
Howe J R
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2001-08-01
Pages
5574-86
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6762644
Subset
IM
Grants
NINDS NIH HHS · NS 37904 · United States
External Links
PubMed source PMC Full Text View journal details
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