Comparison of in vitro and computational experiments on the relation of inter-beat interval and duration of repolarization in a specific type of human induced pluripotent stem cell-derived cardiomyocytes
Autoři:
Philipp Kügler aff001; Georg Rast aff002; Brian D. Guth aff002
Působiště autorů:
Institute of Applied Mathematics and Statistics, Computational Science Lab, University of Hohenheim, Stuttgart, Germany
aff001; Department of Drug Discovery Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany
aff002; Department of Pharmaceutical Sciences, North-West University, Potchefstroom Campus, Potchefstroom, South Africa
aff003
Vyšlo v časopise:
PLoS ONE 14(9)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0221763
Souhrn
We compared a published computational model of the action potential of a specific type of human induced pluripotent stem cell -derived cardiomyocytes (hiPSC-CM) with experimental field potential data with regard to their inter-beat interval and the duration of repolarization. In particular, concomitant changes in inter-beat interval and duration of repolarization were calculated after reduction and/or augmentation of specific ion channel conductances as a surrogate for pharmacological manipulation. The observed mismatches between calculations and experimental data indicate that there is information missing about the cellular test system. Based on our results we hypothesize that, among other currents, the actual If (“funny current”) may deviate from the prediction. We show that replacement of the If formulation by alternative equations causes the model predictions to change qualitatively, however, none of the available formulations is actually achieving a satisfactory match with experimental data. We suggest a strategy to clarify whether the mismatch can be completely resolved at all using single cell models and, if yes, how this goal could be reached.
Klíčová slova:
Research and analysis methods – Simulation and modeling – Mathematical and statistical techniques – Mathematical functions – Curve fitting – Animal studies – Experimental organism systems – Animal models – Rabbits – Biology and life sciences – Physiology – Electrophysiology – Membrane potential – Action potentials – Neurophysiology – Neuroscience – Biochemistry – Proteins – Cell biology – Cellular types – Animal cells – Anatomy – Biological tissue – Organisms – Eukaryota – Animals – Vertebrates – Amniotes – Mammals – Leporids – Medicine and health sciences – Muscle tissue – Muscle cells – Cardiomyocytes – Physical sciences – Physics – Biophysics – Mathematics – Algebra – Polynomials – Computer and information sciences – Data visualization – Infographics – Graphs
Zdroje
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