Source:http://linkedlifedata.com/resource/pubmed/id/19559753
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2009-7-22
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| pubmed:abstractText |
Benign Familial Neonatal Convulsions (BFNC) are a rare epilepsy disorder with an autosomal-dominant inheritance. It is linked to mutations in the potassium channel genes KCNQ2 and KCNQ3. These encode for Kv7.2 and Kv7.3 potassium ion channels, which produce an M-current that regulates the potential firing action in neurons through modulation of the membrane potential. We report on the biophysical and biochemical properties of V589X, T359K and P410fs12X mutant-KCNQ2 ion channels that were detected in three BFNC families. Mutant KCNQ2 cDNAs were co-expressed with WT-KCNQ2 and KCNQ3 cDNAs in HEK293 cells to mimic heterozygous expression of the KCNQ2 mutations in BFNC patients. The resulting potassium currents were measured using patch-clamp techniques and showed an approximately 75% reduction in current and a depolarized shift in the voltage dependence of activation. Furthermore, the time-constant of activation of M-currents in cells expressing T359K and P410fs12X was slower compared to cells expressing only wild-type proteins. Immunofluorescent labeling of HEK293 cells stably expressing GFP-tagged KCNQ2-WT or mutant alpha-subunits indicated cell surface expression of WT, V589X and T359K mutants, suggesting a loss-of-function, while P410fs12X was predominantly retained in the ER and sub-cellular compartments outside the ER suggesting an effectively haplo-insufficient effect.
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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/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/KCNQ2 Potassium Channel,
http://linkedlifedata.com/resource/pubmed/chemical/KCNQ2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/KCNQ3 Potassium Channel,
http://linkedlifedata.com/resource/pubmed/chemical/KCNQ3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
1872-7972
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
2
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| pubmed:volume |
462
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
24-9
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| pubmed:meshHeading |
pubmed-meshheading:19559753-Cell Line,
pubmed-meshheading:19559753-Cell Membrane,
pubmed-meshheading:19559753-Endoplasmic Reticulum,
pubmed-meshheading:19559753-Epilepsy, Benign Neonatal,
pubmed-meshheading:19559753-Family,
pubmed-meshheading:19559753-Female,
pubmed-meshheading:19559753-Fluorescent Antibody Technique,
pubmed-meshheading:19559753-Green Fluorescent Proteins,
pubmed-meshheading:19559753-Humans,
pubmed-meshheading:19559753-KCNQ2 Potassium Channel,
pubmed-meshheading:19559753-KCNQ3 Potassium Channel,
pubmed-meshheading:19559753-Membrane Potentials,
pubmed-meshheading:19559753-Microscopy, Confocal,
pubmed-meshheading:19559753-Microscopy, Fluorescence,
pubmed-meshheading:19559753-Mutation,
pubmed-meshheading:19559753-Mutation, Missense,
pubmed-meshheading:19559753-Patch-Clamp Techniques,
pubmed-meshheading:19559753-Potassium,
pubmed-meshheading:19559753-Time Factors,
pubmed-meshheading:19559753-Transfection
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| pubmed:year |
2009
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| pubmed:articleTitle |
Functional analysis of novel KCNQ2 mutations found in patients with Benign Familial Neonatal Convulsions.
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| pubmed:affiliation |
Complex Genetics Section, DBG-Department of Medical Genetics, University Medical Center Utrecht, The Netherlands.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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