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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2009-10-13
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pubmed:abstractText |
Recently identified genetic forms of short QT syndrome (SQTS) are associated with an increased risk of arrhythmia and sudden death. The SQT3 variant is associated with an amino-acid substitution (D172N) in the KCNJ2-encoded Kir2.1 K+ channel. In this study, whole-cell action potential (AP) clamp recording from transiently transfected Chinese Hamster Ovary cells at 37 degrees C showed marked augmentation of outward Kir2.1 current through D172N channels, associated with right-ward voltage-shifts of peak repolarizing current during both ventricular and atrial AP commands. Peak outward current elicited by ventricular AP commands was inhibited by chloroquine with an IC50 of 2.45 microM for wild-type (WT) Kir2.1, of 3.30 microM for D172N-Kir2.1 alone and of 3.11 microM for co-expressed WT and D172N (P>0.05 for all). These findings establish chloroquine as an effective inhibitor of SQT3 mutant Kir2.1 channels.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19285083-11259572,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19285083-12640008,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19285083-14656705,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19285083-14729380,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19285083-15087421,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19285083-15673388,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19285083-15761194,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19285083-16011830,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19285083-16039272,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19285083-16842817,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19285083-17213921,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19285083-17478540,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19285083-17711440,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19285083-18216262,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19285083-18382206,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19285083-8799888,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19285083-9440706
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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 |
Nov
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pubmed:issn |
1095-8584
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
47
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
743-7
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pubmed:dateRevised |
2010-9-23
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pubmed:meshHeading |
pubmed-meshheading:19285083-Action Potentials,
pubmed-meshheading:19285083-Animals,
pubmed-meshheading:19285083-Antirheumatic Agents,
pubmed-meshheading:19285083-Arrhythmias, Cardiac,
pubmed-meshheading:19285083-CHO Cells,
pubmed-meshheading:19285083-Chloroquine,
pubmed-meshheading:19285083-Cricetinae,
pubmed-meshheading:19285083-Cricetulus,
pubmed-meshheading:19285083-Electrophysiology,
pubmed-meshheading:19285083-Humans,
pubmed-meshheading:19285083-Patch-Clamp Techniques,
pubmed-meshheading:19285083-Potassium Channels, Inwardly Rectifying
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pubmed:year |
2009
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pubmed:articleTitle |
Action potential clamp and chloroquine sensitivity of mutant Kir2.1 channels responsible for variant 3 short QT syndrome.
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pubmed:affiliation |
Department of Physiology and Pharmacology, and Cardiovascular Research Laboratories, School of Medical Sciences, University Walk, University of Bristol, BS8 1TD, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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