Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
1998-9-9
pubmed:abstractText
Zinc inhibits NMDA receptor function through both voltage-dependent and voltage-independent mechanisms. In this report we have investigated the role that the NR1 subunit plays in voltage-independent Zn2+ inhibition. Our data show that inclusion of exon 5 into the NR1 subunit increases the IC50 for voltage-independent Zn2+ inhibition from 3-fold to 10-fold when full length exon 22 is also spliced into the mature NR1 transcript and the NMDA receptor complex contains the NR2A or NR2B subunits; exon 5 has little effect on Zn2+ inhibition of receptors that contain NR2C and NR2D. Mutagenesis within exon 5 indicates that the same residues that control proton inhibition, including Lys211, also control the effects of exon 5 on Zn2+ inhibition. Amino acid exchanges within the NR1 subunit but outside exon 5 (E181Q, E339Q, E342Q, N616R, N616Q, D669N, D669E, C744A, and C798A) that are known to decrease the pH sensitivity also decrease the Zn2+ sensitivity, and concentrations of spermine that relieve tonic proton inhibition also relieve Zn2+ inhibition. In summary, our results define the subunit composition of Zn2+-sensitive NMDA receptors and provide evidence for structural convergence of three allosteric regulators of receptor function: protons, polyamines, and Zn2+.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0270-6474
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6163-75
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Control of voltage-independent zinc inhibition of NMDA receptors by the NR1 subunit.
pubmed:affiliation
Department of Pharmacology, Emory University, Rollins Research Center, Altanta, Georgia 30322, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't