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Acta Physiologica Congress

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Acta Physiologica 2007; Volume 189, Supplement 653
The 86th Annual Meeting of The German Physiological Society
3/25/2007-3/28/2007
Hannover, Germany


LOCAL EXPRESSION IS LOCAL FUNCTION? MODEL ANALYSIS OF SPATIALLY DISTRIBUTED EXPRESSION PATTERNS IN THE HEART AND EXPERIMENTAL VALIDATION
Abstract number: S08-4

Decking1 UKM

1Dept. of Cardiovascular Physiology, Heinrich-Heine-University, Dsseldorf

Within each left ventricular layer there is substantial spatial heterogeneity. At 300 ml resolution, blood flow and energy turnover vary more than 3-fold between individual Low and High flow areas (<60% or >140% of mean flow). Recent data revealed that this heterogeneity also extends to expression of ion channels governing action potential duration (APD). Low flow areas displayed enhanced ERG (3.5-fold) and KChIP2 (2.1-fold) mRNA expression. The encoded proteins mediate resp. govern the repolarizing currents IKr and Ito . To assess the possible effects on APD, a mathematical model translated into CellML and running in the Cellular Open Resource environment was employed. This predicted 1) upon enhanced ERG and 2) upon increased KChIP2 shortening of the APD, 3) an additive effect of the two and 4) the greatest APD prolongation upon ERG blockade in areas of enhanced ERG expression. These predictions were tested and confirmed by epicardial mapping of local QT intervals. This revealed a patchy, temporally stable pattern, a small apico- basal gradient and upon ERG blockade by dofetilide QTi prolongation predominantly in areas of short basal QTi. Thus model analysis facilitated interpretation of expression data and guided their experimental validation.

To cite this abstract, please use the following information:
Acta Physiologica 2007; Volume 189, Supplement 653 :S08-4

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