Key result
An ensemble of parameters from a robust Markov-based model successfully reproduced L-type calcium currents from established human ventricular and Purkinje cell models.
Why the study?
Developing channel-level modeling structures that integrate subcellular and whole-cell models while reproducing diverse experimental data is critical in cardiac electrophysiology, and Markov Chain models are well suited for this purpose.
A novel Markov Chain-based model for L-type calcium currents successfully reproduces human cardiac myocyte electrophysiology, enabling multiscale simulations from subcellular to whole-cell levels.
May aid computational cardiac modeling; leaves open human validation and clinical translation.
The development of modeling structures at the channel level that can integrate subcellular and cell models and properly reproduce different experimental data is of utmost importance in cardiac electrophysiology. In contrast to gate-based models, Markov Chain models are well suited to promote the integration of the subcellular level of the cardiomyocyte to the whole cell. In this paper, we develop Markov Chain models for the L-type Calcium current that can reproduce the electrophysiology of two established human models for the ventricular and Purkinje cells. In addition, instead of presenting a single set of parameters, we present a collection of set of parameters employing Differential Evolution algorithms that can properly reproduce very different protocol data. We show the importance of using an ensemble of a set of parameter values to obtain proper results when considering a second protocol that suppresses calcium inactivation and mimics a pathological condition. We discuss how model discrepancy, data availability, and parameter identifiability can influence the choice of the size of the collection. In summary, we have modified two cardiac models by proposing new Markov Chain models for the L-type Calcium. We keep the original whole-cell dynamics by reproducing the same characteristic action potential and calcium dynamics, whereas the Markov chain-based description of the L-type Calcium channels allows novel small spatial scale simulations of subcellular processes. Finally, the use of collections of parameters was crucial for addressing model discrepancy, identifiability issues, and avoiding fitting parameters overly precisely, i.e., overfitting.
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Novaes et al. (2022) studied Cardiac electrophysiology. Markov Chain-based model vs. Hodgkin-Huxley Gate-based models was evaluated on Fitness function error for reproducing L-type calcium currents. An ensemble of parameters from a robust Markov-based model successfully reproduced L-type calcium currents from established human ventricular and Purkinje cell models.
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