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Cardiovascular Research Advance Access originally published online on November 9, 2007
Cardiovascular Research 2008 77(3):489-496; doi:10.1093/cvr/cvm060
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2007.For permissions please email: journals.permissions@oxfordjournals.org

Spatial heterogeneity of myocardial perfusion predicts local potassium channel expression and action potential duration

Marion Stoll, Michael Quentin, Andrej Molojavyi, Volker Thämer and Ulrich K.M. Decking*

Department of Cardiovascular Physiology, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, Building 22.03,40225 Düsseldorf, Germany

* Corresponding author. Tel: +49 211 81 12651; fax: +49 211 81 12672. E-mail address: decking{at}uni-duesseldorf.de

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 µL 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.

KEYWORDS Ion channels; Gene expression; Action potentials; Coronary circulation; Regional blood flow; Mapping; Microspheres; Computer modelling

Time for primary review: 26 days


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