Document Detail

Spatial heterogeneity of myocardial perfusion predicts local potassium channel expression and action potential duration.
MedLine Citation:
PMID:  18006439     Owner:  NLM     Status:  MEDLINE    
AIMS: In the heart, there is not only a transmural gradient of left ventricular perfusion and action potential duration (APD), but also spatial heterogeneity within each myocardial layer, where local blood flow and energy turnover vary more than three-fold between individual regions. We analysed at high spatial resolution whether a corresponding heterogeneity also extends to ion channel gene expression and APD. METHODS AND RESULTS: In the open-chest beagle dog, left ventricular 300 microL samples of very low or high flow were identified by radioactive microspheres and expression levels determined by quantitative PCR. The distribution of epicardial APD was assessed by mapping local activation repolarization intervals (ARIs) and QT interval (QT). ERG, the potassium channel mediating IKr, and KChIP2, the interacting protein modulating Ito, were increased in Low flow (3.3- and 2.5-fold, P < 0.001 and <0.05, respectively; n = 6 hearts, 30-31 samples each) as compared with High flow areas. This suggested enhanced repolarizing currents in Low flow areas, and in consequence, mathematical model analysis predicted a shorter local APD upon enhanced ERG and IKr. Epicardial mapping revealed a patchy, temporally stable APD pattern (n = 11), a small apico-basal gradient and an APD prolongation induced by the ERG blocker dofetilide predominantly in areas of short basal ARI or QT, respectively (n = 9). In addition, in Short QT areas, ERG expression was three-fold increased (P < 0.05, n = 4). CONCLUSION: The spatial pattern of perfusion is matched by the novel patterns of K+ channel expression and APD. Whenever this newly recognized intramural dispersion of APD increases, it may contribute to arrhythmogenesis.
Marion Stoll; Michael Quentin; Andrej Molojavyi; Volker Thämer; Ulrich K M Decking
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-11-09
Journal Detail:
Title:  Cardiovascular research     Volume:  77     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-01-30     Completed Date:  2008-08-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  489-96     Citation Subset:  IM    
Department of Cardiovascular Physiology, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, Building 22.03,40225 Düsseldorf, Germany.
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MeSH Terms
Action Potentials*
Coronary Circulation*
Ether-A-Go-Go Potassium Channels / genetics*,  physiology
Kv Channel-Interacting Proteins / genetics*,  physiology
Phenethylamines / pharmacology
Sulfonamides / pharmacology
Time Factors
Reg. No./Substance:
0/Ether-A-Go-Go Potassium Channels; 0/Kv Channel-Interacting Proteins; 0/Phenethylamines; 0/Sulfonamides; 115256-11-6/dofetilide

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