Abstract:
:The role of the cardiac current Ik1 in arrhythmogenesis remains highly controversal. To gain further insights into the mechanisms of IK1 involvement in cardiac excitability, we studied the susceptibility of transgenic mice with altered IK1 to arrhythmia during various pharmacological and physiological challenges. Arrhythmogenesis was studied in transgenic mice expressing either dominant negative Kir2.1-AAA or wild type Kir2.1 subunits in the heart, models of IK1 suppression (AAA-TG) and up-regulation (WT-TG), respectively. Under normal conditions, both anesthetized wild type (WT) and AAA-TG mice did not display any spontaneous arrhythmias. In contrast,WT-TG mice displayed numerous arrhythmias of various types. In isolated hearts, the threshold concentration for halothane-induced ventricular tachycardias (VT) was increased to 167% [corrected] in the AAA-TG and decreased to 54% [corrected] in WT-TG hearts when compared to WT hearts. The number of PVCs induced by AV node ablation combined with hypokalemia was reduced in AAA-TG hearts and increased in WT-TG mice. After AV node ablation AAA-TG hearts were more tolerant, and WT-TG less tolerant to isoproterenol- induced arrhythmias than WT hearts. Analysis of monophasic action potentials in isolated hearts shows a significant reduction in the dispersion of action potential repolarization in mice with suppressed IK1. The data strongly support the hypothesis that in the mouse heart upregulation of IK1 is proarrhythmic, and that under certain conditions IK1 blockade in cardiac myocytes may be a potentially useful antiarrhythmic strategy.
journal_name
Basic Res Cardioljournal_title
Basic research in cardiologyauthors
Piao L,Li J,McLerie M,Lopatin ANdoi
10.1007/s00395-007-0659-ysubject
Has Abstractpub_date
2007-09-01 00:00:00pages
416-28issue
5eissn
0300-8428issn
1435-1803journal_volume
102pub_type
杂志文章abstract::Denervation deprives the heart of its normal adrenergic and cholinergic control via the sympathetic and parasympathetic pathways. In a heart which is blood supplied by a donor animal of the same species, normal contractility is maintained, probably by blood borne catecholamines or possibly by unknown inotropic agents ...
journal_title:Basic research in cardiology
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journal_title:Basic research in cardiology
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journal_title:Basic research in cardiology
pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:1992-05-01 00:00:00
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pub_type: 杂志文章
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更新日期:2013-11-01 00:00:00
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pub_type: 临床试验,杂志文章
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:
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pub_type: 杂志文章,评审
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