| Kir3-based inward rectifier potassium current: potential role in atrial tachycardia remodeling effects on atrial repolarization and arrhythmias. | |
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MedLine Citation:
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PMID: 16585394 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: We previously characterized a novel K+ current (IKH) with properties of constitutively active acetylcholine-related current in dog atrium. I(KH) is sensitive to tertiapin-Q (IC50 approximately 10 nmol/L), a highly selective Kir3 current blocker. This study assessed the role of IKH in atrial tachycardia (AT)-remodeled canine left atrium (LA) with the use of tertiapin-Q as a probe. METHODS AND RESULTS: Dogs were subjected to 7 to 13 days of AT (400 bpm). Coronary-perfused LA preparations were studied intact or subjected to cardiomyocyte isolation. IKH was recorded with patch-clamp methods. AT pacing increased time-dependent hyperpolarization-activated current (IKH) at -110 mV from -1.8+/-0.3 (control) to -3.4+/-0.5 pA/pF (AT) and the 100-nmol/L tertiapin-sensitive component from -1.5+/-0.4 (control) to -3.3+/-0.6 pA/pF (AT). Prolonged atrial tachyarrhythmias could be induced with single extrastimuli in AT-remodeled, but not control, preparations, reflecting the atrial fibrillation-promoting effects of AT remodeling. In AT-remodeled preparations, tachyarrhythmia duration averaged 11.0+/-5.2 seconds, with a cycle length of 108+/-6 ms. Tertiapin-Q decreased tachyarrhythmia duration (to 0.6+/-0.1 second; P<0.001) and increased tachyarrhythmia cycle length (to 175+/-10 ms; P<0.001). Atrial action potential duration (APD) was increased 65+/-6% by tertiapin in AT-remodeled hearts versus 19+/-2% (P<0.001) in control. In 2 AT-remodeled preparations, tachyarrhythmia lasted uninterrupted for >20 minutes; tertiapin-Q slowed and then terminated arrhythmia in both. Tertiapin had no effect on left ventricular cardiomyocyte currents or APD. CONCLUSIONS: AT remodeling increases IKH, and a highly selective Kir3 current antagonist, tertiapin-Q, increases APD and suppresses atrial tachyarrhythmias in AT-remodeled preparations without affecting ventricular electrophysiology. Constitutive acetylcholine-related K+ current contributes to AT-remodeling effects in dogs and is a potentially interesting antiarrhythmic target. |
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Authors:
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Tae-Joon Cha; Joachim R Ehrlich; Denis Chartier; Xiao-Yan Qi; Ling Xiao; Stanley Nattel |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-04-03 |
Journal Detail:
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Title: Circulation Volume: 113 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2006 Apr |
Date Detail:
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Created Date: 2006-04-11 Completed Date: 2006-05-18 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
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Languages: eng Pagination: 1730-7 Citation Subset: AIM; IM |
Affiliation:
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Kosin University College of Medicine, Busan, South Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arrhythmias, Cardiac / physiopathology* Atrial Fibrillation / physiopathology* Disease Models, Animal Dogs Electrophysiology G Protein-Coupled Inwardly-Rectifying Potassium Channels / physiology* Heart Atria / physiopathology Tachycardia / physiopathology* Ventricular Remodeling |
| Chemical | |
Reg. No./Substance:
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0/G Protein-Coupled Inwardly-Rectifying Potassium Channels |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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