Location: Single PASMC model (Gosak et al 2014) @ 309a2cd1708e / Doc / README.rst

WeiweiAi <wai484@aucklanduni.ac.nz>
2022-06-13 12:35:09+12:00
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About this model

:Original publication: `Gosak, Marko, et al (2014)`_: "The influence of gap junction network complexity on pulmonary artery smooth muscle reactivity in normoxic and chronically hypoxic conditions." Experimental physiology 99.1 (2014): 272-285.

:DOI: 10.1113/expphysiol.2013.074971

.. _`Gosak, Marko, et al (2014)`: https://doi.org/10.1113/expphysiol.2013.074971

Model status

The current CellML implementation runs in OpenCOR_.
The results have been validated against the data extracted from the figures in the published `Gosak, Marko, et al (2014)`_. We provide the settings used for the figure reproduction with the simulation results shown under ``Experiments``. The model structure can be found in the documentation of ``Components``. The curation process has been summarized in the `Model history`_ and  `Known issues`_.

Model overview
This workspace holds a CellML_ encoding of the `Gosak, Marko, et al (2014)`_ model. 
The `Gosak, Marko, et al (2014)`_ model describes major elements involved in transplasmalemmal ion exchange and intracellular Ca2+ handling, while the mathematical formulation was adapted from the `Parthimos et al.(1999)`_ and `Koenigsberger et al. (2004)`_.

.. _`Parthimos et al.(1999)`: https://doi.org/10.1152/ajpheart.1999.277.3.H1119
.. _`Koenigsberger et al. (2004)`: https://doi.org/10.1529/biophysj.103.037853

.. figure::  Doc/model.jpg
   :width: 70%
   :align: center
   :alt: Schematics of the model

   A diagrammatic representation of the Gosak, Marko, et al (2014) model.

.. _CellML: https://www.cellml.org/

Modular description


CellML divides the mathematical model into distinct components, which are able to be re-used.
The main CellML components are:

- The major elements involved in transplasmalemmal ion exchange, including:
    - Voltage-operated :math:`Ca^{2+}` channels (VOCC): `JVOCCi <Components/JVOCCi.cellml>`_
    - The plasma membrane :math:`Ca^{2+}`-ATPase (PMCA): `JPMCAi <Components/JPMCAi.cellml>`_
    - The :math:`Na^{+}/Ca^{2+}` exchanger (NCX): `JNCXi <Components/JNCXi.cellml>`_
    - The :math:`Na^{+}/K^{+}` ATPase (NKA): `JNKAi <Components/JNKAi.cellml>`_
    - :math:`Ca^{2+}`- and voltage-operated :math:`K^{+}` channels (KC): `JKi <Components/JKi.cellml>`_
    - :math:`Cl^{-}` channels (CC): `JCli <Components/JCli.cellml>`_
- Intracellular Ca2+ handling, including:
    - The sarcoendoplasmic Ca2+-ATPase (SERCA): `JSERCAi <Components/JSERCAi.cellml>`_
    - Calcium Induced Calcium Release (CICR) via the ryanodine receptors: `JCICRi <Components/JCICRi.cellml>`_
    - Basal Ca2+ leak: `Jleaki <Components/Jleaki.cellml>`_
- :math:`Ca^{2+}` concentration in the cytosol (c): `Cai <Components/Cai.cellml>`_
- :math:`Ca^{2+}` concentration in sarcoplasmic reticulum (s): `Casr <Components/Casr.cellml>`_ 
- The dynamics of the cell membrane potential (v): `Vm <Components/Vm.cellml>`_    

Each of these blocks is itself a CellML model, which enables us to reuse the various components in future studies and models.


Following best practices, this model separates the mathematics from the parameterisation of the model. The mathematical model is imported into a specific parameterised instance in order to perform numerical simulations. The default parameters are defined in `Para <Components/Para.cellml>`_.
The parameterisation would include defining the stimulus protocol to be applied.

This workspace encodes `single-cell response to KCl stimulation <Experiments/PASMC_test.cellml/view>`_ and corresponding simulation results.

Simulation settings 
Simulation settings are encoded in SED-ML_ files for experiment execution. It is common that we may need to vary experimental settings to obtain data under various conditions. Hence, the full experimental settings are encoded in the simulation scripts.
The Python scripts to run simulation and reproduce the figures in the original paper are included under the ``Simulation/src`` folder. The ``runSim.ps1`` is used to run the simulation in PowerShell, while ``plotFig4_0.py``, ``plotFig4_1.py``, and ``plotFig4_ci.py`` are ready to plot the figures in the `single-cell response to KCl stimulation <Experiments/PASMC_test.cellml/view>`_.

.. _SED-ML: http://sed-ml.org/

Model history
There is no publicly available code for this model.

Known issues

1. The parameters and initial values listed in Table 1 are not explicitly present in the primary paper. While the model curator used the values from the cited references or assumed some parameters based on the text description, these values may not be the ones that the primary publication used since we could not get confirmation from the original authors. 
.. figure::  Doc/Table1.PNG
   :width: 85%
   :align: center
   :alt: Parameters 

2. The simulation result is not exactly align with the original data, which could be caused by the parameter settings in Table 1.
.. _OpenCOR: https://opencor.ws/