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Updated: Jul 10, 2026
Multiparametric Optical Mapping of the Langendorff-perfused Rabbit Heart
Published on: September 13, 2011
Spatial heterogeneity of myocardial perfusion predicts local potassium channel expression and action potential
Marion Stoll1, Michael Quentin, Andrej Molojavyi
1Department of Cardiovascular Physiology, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, Building 22.03,40225 Düsseldorf, Germany.
Insights
Spatial variations in heart blood flow affect ion channel gene expression and action potential duration (APD). This heterogeneity in K+ channel expression and APD may contribute to cardiac arrhythmias.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Cardiac Electrophysiology
Background:
- Left ventricular (LV) function exhibits transmural gradients in perfusion and action potential duration (APD).
- Significant spatial heterogeneity exists within myocardial layers, with local blood flow and energy turnover varying considerably.
- The extent to which ion channel gene expression and APD mirror this perfusion heterogeneity remains largely unexplored.
Purpose of the Study:
- To investigate if spatial heterogeneity in myocardial perfusion correlates with heterogeneity in ion channel gene expression and APD.
- To analyze the relationship between local blood flow, K+ channel expression (ERG, KChIP2), and epicardial APD at high spatial resolution.
Main Methods:
- Quantitative PCR was used to determine gene expression levels in low-flow and high-flow LV myocardial samples from beagle dogs.
- Radioactive microspheres identified sample regions with distinct perfusion rates.
- Epicardial mapping assessed local activation repolarization intervals (ARIs) and QT intervals (QT) to evaluate APD distribution.
Main Results:
- ERG and KChIP2 expression were significantly increased in low-flow areas compared to high-flow areas (3.3-fold and 2.5-fold, respectively).
- Mathematical modeling predicted shorter local APD in low-flow regions due to enhanced repolarizing currents (IKr).
- Epicardial mapping showed a patchy, stable APD pattern, with ERG expression elevated in short QT areas.
Conclusions:
- A spatial pattern of K+ channel gene expression and APD corresponds to the heterogeneity of myocardial perfusion.
- This newly identified intramural dispersion of APD, driven by perfusion variations, may play a role in arrhythmogenesis.
- Understanding these spatial electrophysiological differences is crucial for comprehending cardiac arrhythmogenesis.
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.
