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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
32
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pubmed:dateCreated |
2006-8-9
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pubmed:abstractText |
Mutations in the cardiac ryanodine receptor 2 (RyR2) have been associated with catecholaminergic polymorphic ventricular tachycardia and a form of arrhythmogenic right ventricular dysplasia. To study the relationship between RyR2 function and these phenotypes, we developed knockin mice with the human disease-associated RyR2 mutation R176Q. Histologic analysis of hearts from RyR2(R176Q/+) mice revealed no evidence of fibrofatty infiltration or structural abnormalities characteristic of arrhythmogenic right ventricular dysplasia, but right ventricular end-diastolic volume was decreased in RyR2(R176Q/+) mice compared with controls, indicating subtle functional impairment due to the presence of a single mutant allele. Ventricular tachycardia (VT) was observed after caffeine and epinephrine injection in RyR2(R176Q/+), but not in WT, mice. Intracardiac electrophysiology studies with programmed stimulation also elicited VT in RyR2(R176Q/+) mice. Isoproterenol administration during programmed stimulation increased both the number and duration of VT episodes in RyR2(R176Q/+) mice, but not in controls. Isolated cardiomyocytes from RyR2(R176Q/+) mice exhibited a higher incidence of spontaneous Ca(2+) oscillations in the absence and presence of isoproterenol compared with controls. Our results suggest that the R176Q mutation in RyR2 predisposes the heart to catecholamine-induced oscillatory calcium-release events that trigger a calcium-dependent ventricular arrhythmia.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16873551-10069797,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16873551-11078270,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16873551-11159936,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16873551-11208676,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16873551-11753384,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16873551-12106942,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16873551-12208807,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16873551-12459180,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16873551-12478303,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16873551-12837242,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16873551-12867510,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16873551-14715535,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16873551-15197150,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16873551-15336972,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16873551-15364613,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16873551-15809371,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16873551-15831148,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16873551-15840485,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16873551-15845383,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16873551-15890976,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16873551-16239587,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16873551-16267250,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16873551-16306448,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16873551-2163219
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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 |
Aug
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pubmed:issn |
0027-8424
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pubmed:author |
pubmed-author:AndersonMark EME,
pubmed-author:CheluMihail GMG,
pubmed-author:DanilaCristina ICI,
pubmed-author:De BiasiMariellaM,
pubmed-author:DirksenRobert TRT,
pubmed-author:GoonasekeraSanjeewa ASA,
pubmed-author:HamiltonSusan LSL,
pubmed-author:KannankerilPrince JPJ,
pubmed-author:KearneyDebra LDL,
pubmed-author:MitchellBrett MBM,
pubmed-author:PautlerRobia GRG,
pubmed-author:RodenDan MDM,
pubmed-author:SoodSubeenaS,
pubmed-author:TaffetGeorge EGE,
pubmed-author:WehrensXander H TXH,
pubmed-author:ZhangWeiW
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pubmed:issnType |
Print
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pubmed:day |
8
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pubmed:volume |
103
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
12179-84
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pubmed:dateRevised |
2011-10-18
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pubmed:meshHeading |
pubmed-meshheading:16873551-Animals,
pubmed-meshheading:16873551-Caffeine,
pubmed-meshheading:16873551-Cardiomyopathies,
pubmed-meshheading:16873551-Catecholamines,
pubmed-meshheading:16873551-Central Nervous System Stimulants,
pubmed-meshheading:16873551-Epinephrine,
pubmed-meshheading:16873551-Genetic Predisposition to Disease,
pubmed-meshheading:16873551-Male,
pubmed-meshheading:16873551-Mice,
pubmed-meshheading:16873551-Mice, Transgenic,
pubmed-meshheading:16873551-Mutation,
pubmed-meshheading:16873551-Myocardium,
pubmed-meshheading:16873551-Ryanodine Receptor Calcium Release Channel,
pubmed-meshheading:16873551-Tachycardia, Ventricular,
pubmed-meshheading:16873551-Vasoconstrictor Agents
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pubmed:year |
2006
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pubmed:articleTitle |
Mice with the R176Q cardiac ryanodine receptor mutation exhibit catecholamine-induced ventricular tachycardia and cardiomyopathy.
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pubmed:affiliation |
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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