Source:http://linkedlifedata.com/resource/pubmed/id/12967988
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
23
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| pubmed:dateCreated |
2003-9-11
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| pubmed:abstractText |
Modulation of voltage-gated sodium channels (VGSC) can have a major impact on cell excitability. Analysis of calmodulin (CaM) binding to GST-fusion proteins containing the C-terminal domains of Nav1.1-Nav1.9 indicates that some of the tetrodotoxin-sensitive VGSC isoforms, including NaV1.4 and NaV1.6, are able to bind CaM in a calcium-independent manner. Here we demonstrate that association with CaM is important for functional expression of NaV1.4 and NaV1.6 VGSCs. Disrupting the interaction between CaM and the C terminus of NaV1.4 and NaV1.6 channels reduced current amplitude by 99 and 62%, respectively. Overexpression of CaM increased the current generated by Nav1.4 and Nav1.6 C-terminal mutant constructs that exhibited intermediate current densities and intermediate binding affinities for CaM, demonstrating that this effect on current density was directly dependent on the ability of the C terminus to bind CaM. In addition to the effects on current density, calmodulin also was able to modulate the inactivation kinetics of Nav1.6, but not Nav1.4, currents in a calcium-dependent manner. Our data demonstrate that CaM can regulate the properties of VGSCs via calcium-dependent and calcium-independent mechanisms and suggest that modulation of neuronal sodium channels may play a role in calcium-dependent neuronal plasticity.
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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/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calmodulin,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/SCN8A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Scn8a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium Channels
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
1529-2401
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| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:day |
10
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| pubmed:volume |
23
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
8261-70
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:12967988-Amino Acid Motifs,
pubmed-meshheading:12967988-Animals,
pubmed-meshheading:12967988-Biolistics,
pubmed-meshheading:12967988-Calcium,
pubmed-meshheading:12967988-Calmodulin,
pubmed-meshheading:12967988-Cells, Cultured,
pubmed-meshheading:12967988-Humans,
pubmed-meshheading:12967988-Kidney,
pubmed-meshheading:12967988-Kinetics,
pubmed-meshheading:12967988-Mice,
pubmed-meshheading:12967988-Mutagenesis, Site-Directed,
pubmed-meshheading:12967988-Nerve Tissue Proteins,
pubmed-meshheading:12967988-Neurons,
pubmed-meshheading:12967988-Patch-Clamp Techniques,
pubmed-meshheading:12967988-Protein Binding,
pubmed-meshheading:12967988-Protein Isoforms,
pubmed-meshheading:12967988-Rats,
pubmed-meshheading:12967988-Signal Transduction,
pubmed-meshheading:12967988-Sodium Channels
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| pubmed:year |
2003
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| pubmed:articleTitle |
Calmodulin binds to the C terminus of sodium channels Nav1.4 and Nav1.6 and differentially modulates their functional properties.
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| pubmed:affiliation |
Department of Neurology and Paralyzed Veterans of America/Eastern Paralyzed Veterans Association Neuroscience Research Center, Yale School of Medicine, New Haven, Connecticut 06510, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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