Transmural cellular heterogeneity in myocardial electromechanics
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Myocardial heterogeneity is an attribute of the normal heart. We have developed integrative models of cardiomyocytes from the subendocardial (ENDO) and subepicardial (EPI) ventricular regions that take into account experimental data on specific regional features of intracellular electromechanical coupling in the guinea pig heart. The models adequately simulate experimental data on the differences in the action potential and contraction between the ENDO and EPI cells. The modeling results predict that heterogeneity in the parameters of calcium handling and myofilament mechanics in isolated ENDO and EPI cardiomyocytes are essential to produce the differences in Ca2+ transients and contraction profiles via cooperative mechanisms of mechano-calcium-electric feedback and may further slightly modulate transmural differences in the electrical properties between the cells. Simulation results predict that ENDO cells have greater sensitivity to changes in the mechanical load than EPI cells. These data are important for understanding the behavior of cardiomyocytes in the intact heart.
KeywordsCardiac transmural heterogeneity Electromechanical coupling Mechano-calcium-electric feedback Cardiac modeling Cardiomyocyte
This work was supported by RF Government Resolution #211 of March 16, 2013 and Program of the RAS Presidium #I.33П.
AK, NB-V: conception of the mathematical models, computational simulations, design, analysis and interpretation of the computational experiments. LK, OS: conception of the mathematical models, design, analysis and interpretation of the computational experiments. GI: analysis and interpretation of the computational experiments. The manuscript was written by AK and OS, with the assistance of NB-V, LK, GI. All authors approved the final version of the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest related to this study.
This article does not contain any studies with human participants or animals performed by any of the authors.
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