Source:http://linkedlifedata.com/resource/pubmed/id/15271672
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
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| pubmed:dateCreated |
2004-11-19
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| pubmed:abstractText |
To assess the functional significance of upregulation of the cardiac current (IK1), we have produced and characterized the first transgenic (TG) mouse model of IK1 upregulation. To increase IK1 density, a pore-forming subunit of the Kir2.1 (green fluorescent protein-tagged) channel was expressed in the heart under control of the alpha-myosin heavy chain promoter. Two lines of TG animals were established with a high level of TG expression in all major parts of the heart: line 1 mice were characterized by 14% heart hypertrophy and a normal life span; line 2 mice displayed an increased mortality rate, and in mice < or =1 mo old, heart weight-to-body weight ratio was increased by >100%. In adult ventricular myocytes expressing the Kir2.1-GFP subunit, IK1 conductance at the reversal potential was increased approximately 9- and approximately 10-fold in lines 1 and 2, respectively. Expression of the Kir2.1 transgene in line 2 ventricular myocytes was heterogeneous when assayed by single-cell analysis of GFP fluorescence. Surface ECG recordings in line 2 mice revealed numerous abnormalities of excitability, including slowed heart rate, premature ventricular contractions, atrioventricular block, and atrial fibrillation. Line 1 mice displayed a less severe phenotype. In both TG lines, action potential duration at 90% repolarization and monophasic action potential at 75-90% repolarization were significantly reduced, leading to neuronlike action potentials, and the slow phase of the T wave was abolished, leading to a short Q-T interval. This study provides a new TG model of IK1 upregulation, confirms the significant role of IK1 in cardiac excitability, and is consistent with adverse effects of IK1 upregulation on cardiac electrical activity.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
0363-6135
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
287
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
H2790-802
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:15271672-Action Potentials,
pubmed-meshheading:15271672-Animals,
pubmed-meshheading:15271672-Atrial Fibrillation,
pubmed-meshheading:15271672-Cardiomegaly,
pubmed-meshheading:15271672-Electrocardiography,
pubmed-meshheading:15271672-Flow Cytometry,
pubmed-meshheading:15271672-Gene Expression,
pubmed-meshheading:15271672-Green Fluorescent Proteins,
pubmed-meshheading:15271672-Heart Block,
pubmed-meshheading:15271672-Mice,
pubmed-meshheading:15271672-Mice, Inbred C57BL,
pubmed-meshheading:15271672-Mice, Transgenic,
pubmed-meshheading:15271672-Myocytes, Cardiac,
pubmed-meshheading:15271672-Potassium,
pubmed-meshheading:15271672-Potassium Channels, Inwardly Rectifying,
pubmed-meshheading:15271672-Up-Regulation
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| pubmed:year |
2004
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| pubmed:articleTitle |
Transgenic upregulation of IK1 in the mouse heart leads to multiple abnormalities of cardiac excitability.
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| pubmed:affiliation |
Dept. of Molecular and Integrative Physiology, Univ. of Michigan, Rm. 7812 Medical Science II, 1150 W. Medical Center Dr., Ann Arbor, MI 48109, 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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