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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2002-1-10
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pubmed:abstractText |
The muscarinic-regulated potassium current (M-current), formed by the heteromeric assembly of subunits encoded by the KCNQ2 and KCNQ3 genes, is a primary regulator of neuronal excitability; this regulation is accomplished by impeding repetitive firing and causing spike-frequency adaptation. Mutations in KCNQ2 or KCNQ3 cause benign familial neonatal convulsions (BFNC), a rare autosomal-dominant generalized epilepsy of newborns, by reducing the maximal current carried by the M-channels without affecting ion selectivity or gating properties. Here we show that KCNQ2/KCNQ3 channels carrying a novel BFNC-causing mutation leading to an arginine to tryptophan substitution in the voltage-sensing S4 domain of KCNQ2 subunits (R214W) displayed slower opening and faster closing kinetics and a decreased voltage sensitivity with no concomitant changes in maximal current or plasma membrane expression. These results suggest that mutation-induced gating alterations of the M-current may cause epilepsy in neonates.
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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 |
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,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels, Voltage-Gated,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Subunits
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1529-2401
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
22
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
RC199
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11784811-Amino Acid Substitution,
pubmed-meshheading:11784811-Animals,
pubmed-meshheading:11784811-Cell Membrane,
pubmed-meshheading:11784811-Cells, Cultured,
pubmed-meshheading:11784811-Epilepsy, Benign Neonatal,
pubmed-meshheading:11784811-Gene Expression,
pubmed-meshheading:11784811-Genes, Dominant,
pubmed-meshheading:11784811-Humans,
pubmed-meshheading:11784811-Ion Channel Gating,
pubmed-meshheading:11784811-Italy,
pubmed-meshheading:11784811-KCNQ2 Potassium Channel,
pubmed-meshheading:11784811-KCNQ3 Potassium Channel,
pubmed-meshheading:11784811-Microinjections,
pubmed-meshheading:11784811-Mutagenesis, Site-Directed,
pubmed-meshheading:11784811-Mutation,
pubmed-meshheading:11784811-Oocytes,
pubmed-meshheading:11784811-Patch-Clamp Techniques,
pubmed-meshheading:11784811-Pedigree,
pubmed-meshheading:11784811-Potassium,
pubmed-meshheading:11784811-Potassium Channels,
pubmed-meshheading:11784811-Potassium Channels, Voltage-Gated,
pubmed-meshheading:11784811-Protein Structure, Tertiary,
pubmed-meshheading:11784811-Protein Subunits,
pubmed-meshheading:11784811-Structure-Activity Relationship,
pubmed-meshheading:11784811-Xenopus
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pubmed:year |
2002
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pubmed:articleTitle |
Benign familial neonatal convulsions caused by altered gating of KCNQ2/KCNQ3 potassium channels.
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pubmed:affiliation |
Division of Pharmacology, Department of Neuroscience, School of Medicine, University of Naples Federico II, 80131 Naples, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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