Document Detail

Kir3-based inward rectifier potassium current: potential role in atrial tachycardia remodeling effects on atrial repolarization and arrhythmias.
MedLine Citation:
PMID:  16585394     Owner:  NLM     Status:  MEDLINE    
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.
Tae-Joon Cha; Joachim R Ehrlich; Denis Chartier; Xiao-Yan Qi; Ling Xiao; Stanley Nattel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-04-03
Journal Detail:
Title:  Circulation     Volume:  113     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-04-11     Completed Date:  2006-05-18     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1730-7     Citation Subset:  AIM; IM    
Kosin University College of Medicine, Busan, South Korea.
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MeSH Terms
Arrhythmias, Cardiac / physiopathology*
Atrial Fibrillation / physiopathology*
Disease Models, Animal
G Protein-Coupled Inwardly-Rectifying Potassium Channels / physiology*
Heart Atria / physiopathology
Tachycardia / physiopathology*
Ventricular Remodeling
Reg. No./Substance:
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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