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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
2001-9-4
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pubmed:abstractText |
Deletion of amino-acid residues 1505-1507 (KPQ) in the cardiac SCN5A Na(+) channel causes autosomal dominant prolongation of the electrocardiographic QT interval (long-QT syndrome type 3 or LQT3). Excessive prolongation of the action potential at low heart rates predisposes individuals with LQT3 to fatal arrhythmias, typically at rest or during sleep. Here we report that mice heterozygous for a knock-in KPQ-deletion (SCN5A(Delta/+)) show the essential LQT3 features and spontaneously develop life-threatening polymorphous ventricular arrhythmias. Unexpectedly, sudden accelerations in heart rate or premature beats caused lengthening of the action potential with early afterdepolarization and triggered arrhythmias in Scn5a(Delta/+) mice. Adrenergic agonists normalized the response to rate acceleration in vitro and suppressed arrhythmias upon premature stimulation in vivo. These results show the possible risk of sudden heart-rate accelerations. The Scn5a(Delta/+) mouse with its predisposition for pacing-induced arrhythmia might be useful for the development of new treatments for the LQT3 syndrome.
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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 |
Sep
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pubmed:issn |
1078-8956
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pubmed:author |
pubmed-author:BenndorfKK,
pubmed-author:CarmelietEE,
pubmed-author:CarmelietPP,
pubmed-author:ClancyC ECE,
pubmed-author:CollenDD,
pubmed-author:CompernolleVV,
pubmed-author:DewerchinMM,
pubmed-author:DugarmaaSS,
pubmed-author:FlamengWW,
pubmed-author:MoontMM,
pubmed-author:NuyensDD,
pubmed-author:RossenbackerTT,
pubmed-author:RudR CRC,
pubmed-author:RudaAA,
pubmed-author:SmithJ SJS,
pubmed-author:StenglMM
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pubmed:issnType |
Print
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pubmed:volume |
7
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1021-7
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pubmed:dateRevised |
2011-7-22
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pubmed:meshHeading |
pubmed-meshheading:11533705-Adrenergic beta-Agonists,
pubmed-meshheading:11533705-Animals,
pubmed-meshheading:11533705-Arrhythmias, Cardiac,
pubmed-meshheading:11533705-Cardiac Pacing, Artificial,
pubmed-meshheading:11533705-Electrocardiography,
pubmed-meshheading:11533705-Humans,
pubmed-meshheading:11533705-Isoproterenol,
pubmed-meshheading:11533705-Long QT Syndrome,
pubmed-meshheading:11533705-Membrane Potentials,
pubmed-meshheading:11533705-Mice,
pubmed-meshheading:11533705-Mice, Mutant Strains,
pubmed-meshheading:11533705-Myocardium,
pubmed-meshheading:11533705-Sequence Deletion,
pubmed-meshheading:11533705-Sodium,
pubmed-meshheading:11533705-Sodium Channels
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pubmed:year |
2001
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pubmed:articleTitle |
Abrupt rate accelerations or premature beats cause life-threatening arrhythmias in mice with long-QT3 syndrome.
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pubmed:affiliation |
Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, KU Leuven, Leuven, Belgium.
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pubmed:publicationType |
Journal Article
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