An ensemble of parameters from a robust Markov-based model reproduces L-type calcium currents from different human cardiac myocytes
Visualitza/Obre
10.1371/journal.pone.0266233
Inclou dades d'ús des de 2022
Cita com:
hdl:2117/366299
Tipus de documentArticle
Data publicació2022-04-05
EditorPublic Library of Science (PLOS)
Condicions d'accésAccés obert
Llevat que s'hi indiqui el contrari, els
continguts d'aquesta obra estan subjectes a la llicència de Creative Commons
:
Reconeixement-NoComercial-SenseObraDerivada 3.0 Espanya
Abstract
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.
CitacióMontes, G. [et al.]. An ensemble of parameters from a robust Markov-based model reproduces L-type calcium currents from different human cardiac myocytes. "PloS one", 5 Abril 2022, vol. 17, núm. 4, p. 0266233:1-0266233:26.
ISSN1932-6203
Fitxers | Descripció | Mida | Format | Visualitza |
---|---|---|---|---|
an_ensemble_of_parameters.pdf | 16,84Mb | Visualitza/Obre |