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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
16
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pubmed:dateCreated |
1998-9-9
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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+.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Recombinant,
http://linkedlifedata.com/resource/pubmed/chemical/Polyamines,
http://linkedlifedata.com/resource/pubmed/chemical/Protons,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, N-Methyl-D-Aspartate,
http://linkedlifedata.com/resource/pubmed/chemical/Spermine,
http://linkedlifedata.com/resource/pubmed/chemical/Zinc
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0270-6474
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6163-75
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9698310-Animals,
pubmed-meshheading:9698310-DNA, Recombinant,
pubmed-meshheading:9698310-Electrophysiology,
pubmed-meshheading:9698310-Exons,
pubmed-meshheading:9698310-Female,
pubmed-meshheading:9698310-Mutation,
pubmed-meshheading:9698310-Oocytes,
pubmed-meshheading:9698310-Polyamines,
pubmed-meshheading:9698310-Protons,
pubmed-meshheading:9698310-Receptors, N-Methyl-D-Aspartate,
pubmed-meshheading:9698310-Spermine,
pubmed-meshheading:9698310-Xenopus laevis,
pubmed-meshheading:9698310-Zinc
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pubmed:year |
1998
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pubmed:articleTitle |
Control of voltage-independent zinc inhibition of NMDA receptors by the NR1 subunit.
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pubmed:affiliation |
Department of Pharmacology, Emory University, Rollins Research Center, Altanta, Georgia 30322, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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