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- Marbán Eduardo
- Institute of Molecular Cardiobiology, The Johns Hopkins University
書誌事項
- タイトル別名
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- Oita International Electrocardiology Symposium 2000 “Electrophysiology and Management of Lethal Arrhythmias in the New Millennium: From Genes to Bedside”
- Molecular dissection of cardiac repolarization
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抄録
Repolarization of the cardiac ventricles is a complex process involving the decay of inward currents and the resurgence of outward currents, most of which are carried by potassium channels. At least ten different genes contribute subunits to cardiac K channels, but the relative roles of the various gene products in repolarization remains uncertain. To investigate this question, my laboratory has overexpressed defined ion channel genes within the ventricle. Wild-type genes are expressed to gauge the electrophysiological effects of enhancing a given K channel subunit, whereas mutant dominant-negative constructs enable assessment of the functional consequences of gene suppression. The lecture upon which this extended abstract is based covers a variety of gene products; the present publication summarizes work in the public domain, focusing on the Ca2+-independent transient outward current (Itol) and the underlying Kv4 gene family. This current is markedly decreased in heart failure, possibly contributing to unstable repolarization in that disease state. We injected adenovirus vectors in vivo to overexpress or to suppress Ito1 in guineapigs and rats, respectively. Overexpression of wild-type Kv4.3 accelerated repolarization in guinea pigs, which lack this current; conversely, a dominant-negative Kv4.3 construct suppressed Ito1, while prolonging action potentials and QT intervals in rats. Thus, Itol plays a crucial role in setting the plateau potential and overall APD, supporting a causative role for suppression of this current in the electrophysiological alterations of heart failure. The electrocardiographic findings indicate that somatic gene transfer can be used to create gene-specific animal models of the long QT syndrome.
収録刊行物
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- 心電図
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心電図 20 (Suppl3), 117-119, 2000
一般社団法人 日本不整脈心電学会
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詳細情報 詳細情報について
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- CRID
- 1390282679748855680
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- NII論文ID
- 10008114214
- 130004087459
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- NII書誌ID
- AN00358282
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- ISSN
- 18842437
- 02851660
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- データソース種別
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- JaLC
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- 抄録ライセンスフラグ
- 使用不可