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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6923
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pubmed:dateCreated |
2003-2-6
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pubmed:abstractText |
Mutations in ion channels involved in the generation and termination of action potentials constitute a family of molecular defects that underlie fatal cardiac arrhythmias in inherited long-QT syndrome. We report here that a loss-of-function (E1425G) mutation in ankyrin-B (also known as ankyrin 2), a member of a family of versatile membrane adapters, causes dominantly inherited type 4 long-QT cardiac arrhythmia in humans. Mice heterozygous for a null mutation in ankyrin-B are haploinsufficient and display arrhythmia similar to humans. Mutation of ankyrin-B results in disruption in the cellular organization of the sodium pump, the sodium/calcium exchanger, and inositol-1,4,5-trisphosphate receptors (all ankyrin-B-binding proteins), which reduces the targeting of these proteins to the transverse tubules as well as reducing overall protein level. Ankyrin-B mutation also leads to altered Ca2+ signalling in adult cardiomyocytes that results in extrasystoles, and provides a rationale for the arrhythmia. Thus, we identify a new mechanism for cardiac arrhythmia due to abnormal coordination of multiple functionally related ion channels and transporters.
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pubmed:commentsCorrections |
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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/ANK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ank2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ankyrins,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/ITPR1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Calcium Exchanger,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Potassium-Exchanging ATPase
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0028-0836
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pubmed:author |
pubmed-author:AliMervat EME,
pubmed-author:BennettVannV,
pubmed-author:DillyKeith WKW,
pubmed-author:EscandeDenisD,
pubmed-author:GramoliniAnthony OAO,
pubmed-author:GuatimosimSilviaS,
pubmed-author:HaurognéKarineK,
pubmed-author:KyndtFlorenceF,
pubmed-author:Le MarecHerveH,
pubmed-author:LedererW JWJ,
pubmed-author:MohlerPeter JPJ,
pubmed-author:RogersTerry BTB,
pubmed-author:SchottJean-JacquesJJ,
pubmed-author:SongLong-ShengLS,
pubmed-author:duBellWilliam HWH
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pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
421
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
634-9
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:12571597-Action Potentials,
pubmed-meshheading:12571597-Animals,
pubmed-meshheading:12571597-Ankyrins,
pubmed-meshheading:12571597-Bradycardia,
pubmed-meshheading:12571597-Calcium Channels,
pubmed-meshheading:12571597-Calcium Signaling,
pubmed-meshheading:12571597-Death, Sudden, Cardiac,
pubmed-meshheading:12571597-Electrocardiography,
pubmed-meshheading:12571597-Female,
pubmed-meshheading:12571597-Heart,
pubmed-meshheading:12571597-Heart Rate,
pubmed-meshheading:12571597-Heterozygote,
pubmed-meshheading:12571597-Humans,
pubmed-meshheading:12571597-Inositol 1,4,5-Trisphosphate Receptors,
pubmed-meshheading:12571597-Long QT Syndrome,
pubmed-meshheading:12571597-Male,
pubmed-meshheading:12571597-Mice,
pubmed-meshheading:12571597-Mutation,
pubmed-meshheading:12571597-Myocardium,
pubmed-meshheading:12571597-Patch-Clamp Techniques,
pubmed-meshheading:12571597-Pedigree,
pubmed-meshheading:12571597-Phenotype,
pubmed-meshheading:12571597-Protein Binding,
pubmed-meshheading:12571597-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:12571597-Sodium-Calcium Exchanger,
pubmed-meshheading:12571597-Sodium-Potassium-Exchanging ATPase
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pubmed:year |
2003
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pubmed:articleTitle |
Ankyrin-B mutation causes type 4 long-QT cardiac arrhythmia and sudden cardiac death.
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pubmed:affiliation |
Howard Hughes Medical Institute and Departments of Cell Biology, Biochemistry, and Neuroscience, Duke University Medical Center, Durham, North Carolina 27710, 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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