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rdf:type |
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lifeskim:mentions |
umls-concept:C0006104,
umls-concept:C0027746,
umls-concept:C0033727,
umls-concept:C0205263,
umls-concept:C0332157,
umls-concept:C0332281,
umls-concept:C0392747,
umls-concept:C0439799,
umls-concept:C0597484,
umls-concept:C1515877,
umls-concept:C1709915,
umls-concept:C1879547
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pubmed:issue |
46
|
|
pubmed:dateCreated |
1998-12-8
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|
pubmed:abstractText |
BNC1 is a mammalian neuronal cation channel in the novel DEG/ENaC ion channel family. BNC1 channels are transiently activated by extracellular protons and are constitutively activated by insertion of large residues, such as valine, in place of Gly-430; residue 430 is a site where analogous mutations in some Caenorhabditis elegans family members cause a swelling neurodegeneration. Mutation of Gly-430 to a small amino acid, cysteine, neither generated constitutive currents nor allowed modification of this residue by sulfhydryl-reactive methanethiosulfonate (MTS) compounds. However, when protons activated the channel, Cys-430 became accessible to extracellular MTS reagents, which modified Cys-430 to generate constitutive currents. Fluorescent MTS reagents also labeled Cys-430 in activated channels. These data indicate that protons induce a reversible conformational change that activates BNC1 thereby exposing residue 430 to the extracellular solution. Once Cys-430 is modified with a large chemical group, the channel is prevented from relaxing back to the inactive state. These results link ligand-dependent activation and activation by mutations that cause neurodegeneration.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0021-9258
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pubmed:author |
|
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pubmed:issnType |
Print
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pubmed:day |
13
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pubmed:volume |
273
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
30204-7
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:9804777-Amino Acid Substitution,
pubmed-meshheading:9804777-Animals,
pubmed-meshheading:9804777-Cold Temperature,
pubmed-meshheading:9804777-Epithelial Sodium Channel,
pubmed-meshheading:9804777-Ethyl Methanesulfonate,
pubmed-meshheading:9804777-Female,
pubmed-meshheading:9804777-Indicators and Reagents,
pubmed-meshheading:9804777-Ion Channel Gating,
pubmed-meshheading:9804777-Ion Channels,
pubmed-meshheading:9804777-Mesylates,
pubmed-meshheading:9804777-Mutation,
pubmed-meshheading:9804777-Nerve Tissue Proteins,
pubmed-meshheading:9804777-Neurodegenerative Diseases,
pubmed-meshheading:9804777-Neurons,
pubmed-meshheading:9804777-Oocytes,
pubmed-meshheading:9804777-Protein Conformation,
pubmed-meshheading:9804777-Sodium Channels,
pubmed-meshheading:9804777-Structure-Activity Relationship,
pubmed-meshheading:9804777-Xenopus laevis
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pubmed:year |
1998
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|
pubmed:articleTitle |
Protons activate brain Na+ channel 1 by inducing a conformational change that exposes a residue associated with neurodegeneration.
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|
pubmed:affiliation |
Howard Hughes Medical Institute, Departments of Internal Medicine and Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, Iowa 52242, 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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