- Author:
- nima <nafs080@aucklanduni.ac.nz>
- Date:
- 2022-02-03 22:14:50+13:00
- Desc:
- updated overview.srt
- Permanent Source URI:
- https://staging.physiomeproject.org/workspace/702/rawfile/a0bf492b6e68947d32caf1e4f2d77efa59ce1bb4/Fig4.rst
About this model
====================
:Original publication: `Kernik et al. (2019)`_:
"A computational model of induced pluripotent stem-cell derived cardiomyocytes
incorporating experimental variability from multiple data sources" J Physiol. 2019 Sep 1; 597(17): 4533-4564.
:DOI: https://dx.doi.org/10.1113%2FJP277724
.. _`Kernik et al. (2019)`: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767694/
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Figure 04
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Rapid delayed rectifier potassium current (:math:`I_Kr`) model optimization
****************************************************************************
The voltage dependent activation and inactivation gating variables were modeled here.
The single exponential voltage-dependent rate constant model
was optimized to fit the voltage dependence of :math:`I_Kr` inactivation in the `ten
Tusscher 2004 model`_. The result of inactivation gating is shown in Fig. 4 A and D.
Activation gating model were fit to four different data for multiple labs; `Ma et al. (2011)`_,
`Garg et al. (2018)`_, `Bellin et al. (2013)`_ and `Es-Salah-Lamoureux et al. (2016)`_.
Parameters in `Ma et al. (2011)`_, `Garg et al. (2018)`_ and `Es-Salah-Lamoureux et al. (2016)`_.
model, were optimized using the time constant activation of `Ma et al. (2011)`_. Time
constant activation in `Bellin et al. (2013)`_ were used in the model. (Fig. 4 C)
I-V curve for :math:`I_Kr` shows in Fig. 4 B.
`Current_Ikr.cellml`_ is the main CellML files which has all the formulation for rapid delayed rectifier potassium current,
Its associated Sedml file contains all the simulation settings.
All the CellML files and SED-ML files related to this channel need to be downloaded in a same folder (Current_Ikr, gating_Ikr, parameter_Ikr, parameter, unit)
as well as python script (`fig4.py`_). In the python script, required Sedml file (Current_Ikr.sedml) is loaded
into the script and by running the code following figure is reproduced. fig4.py is used to
generate the simulation and reproduces the graph shown in Figure 5 in the original study.
In order to reproduce Figure 5, once all the files are downloaded to the same folder,
execute the following script from the command line (command prompt):
cd [PathToThisFile]
[PathToOpenCOR]/pythonshell fig4.py
.. figure:: Figure04.png
:width: 85%
:align: center
:alt: Rapid delayed rectifier potassium current model optimization
A, optimized activation with dataset-specific model fits. Different colour represent experimental
iPSC-CM data from multiple laboratories. B, I-V curve, C, Time constant of :math:`I_Kr` activation gate. D,
Time constant of :math:`I_Kr` inactivation gate.
.. _`ten Tusscher 2004 model`: https://journals.physiology.org/doi/full/10.1152/ajpheart.00794.2003/
.. _`Ma et al. (2011)`: https://pubmed.ncbi.nlm.nih.gov/21890694/
.. _`Garg et al. (2018)`: https://www.jacc.org/doi/abs/10.1016/j.jacc.2018.04.041
.. _`Bellin et al. (2013)`: https://www.nature.com/articles/srep30967/https://www.embopress.org/doi/full/10.1038/emboj.2013.240
.. _Es-Salah-Lamoureux et al. (2016): https://pubmed.ncbi.nlm.nih.gov/27590098/
.. _`Current_Ikr.cellml`: https://models.physiomeproject.org/workspace/702/rawfile/a619946dc2f89d6d787cebfbd9b1f2a54f5aa227/Current_Ikr.cellml
.. _`fig4.py`: https://models.physiomeproject.org/workspace/702/rawfile/a619946dc2f89d6d787cebfbd9b1f2a54f5aa227/fig4.py
