- Author:
- WeiweiAi <wai484@aucklanduni.ac.nz>
- Date:
- 2022-06-15 11:08:09+12:00
- Desc:
- Include simFig3
- Permanent Source URI:
- https://models.cellml.org/workspace/874/rawfile/eb9b6ae068716f451953bd5900bcfdaa5761b0cf/Doc/README.rst
About this model
====================
:Original publication: `Koenigsberger, Michèle, et al. (2004)`_: "Ca2+ dynamics in a population of smooth muscle cells: modeling the recruitment and synchronization." Biophysical journal 87.1 (2004): 92-104.
:DOI: 10.1529/biophysj.103.037853
.. _`Koenigsberger, Michèle, et al. (2004)`: https://doi.org/10.1529/biophysj.103.037853
Model status
=============
The current CellML implementation runs in OpenCOR_.
The results have been validated against the data extracted from the figures in the published `Koenigsberger, Michèle, et al. (2004)`_. 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
===================
The `Koenigsberger, Michèle, et al. (2004)`_ proposed a model describing a population of coupled smooth muscle cells (SMCs), while the calcium dynamics in a single SMC extended the model of `Parthimos et al.(1999)`_. This workspace holds a CellML_ encoding of the `Koenigsberger, Michèle, et al. (2004)`_ single SMC model.
.. _`Parthimos et al.(1999)`: https://doi.org/10.1152/ajpheart.1999.277.3.H1119
.. _`Gosak, Marko, et al (2014)`: https://doi.org/10.1113/expphysiol.2013.074971
.. _`Single PASMC model (Gosak et al 2014)`: https://models.physiomeproject.org/workspace/83f
.. _CellML: https://www.cellml.org/
Modular description
====================
Components
-----------
CellML divides the mathematical model into distinct components, which are able to be re-used. Since we have implemented the `Gosak, Marko, et al (2014)`_ model, which was also based on the mathematical formulation of the `Koenigsberger, Michèle, et al. (2004)`_ model, we reuse some existing components defined in the workspace `Single PASMC model (Gosak et al 2014)`_. However, the definition of some flux directions are different, we modify the signs in corresponding terms to reflect it.
The main CellML components are:
- The major elements involved in transplasmalemmal ion exchange, including:
- The calcium influx through Voltage-operated :math:`Ca^{2+}` channels (VOCC): reuse the component `JVOCCi <SinglePASMC/Components/JVOCCi.cellml>`_ that has an opposite direction.
- The calcium extrusion by :math:`Ca^{2+}`-ATPase pumps, :math:`J_{extrusion}` : reuse the component `JPMCAi <SinglePASMC/Components/JPMCAi.cellml>`_ that has the same definition.
- The :math:`Na^{+}/Ca^{2+}` exchange :math:`J_{Na/Cai}` : reuse the component `JNCXi <SinglePASMC/Components/JNCXi.cellml>`_ that has an opposite direction.
- The flux through :math:`Na^{+}/K^{+}` ATPase : the `JNKAi <SinglePASMC/Components/JNKAi.cellml>`_ definition in the `Gosak, Marko, et al (2014)`_ model is different from the `Koenigsberger, Michèle, et al. (2004)`_ model, hence this component is newly defined in `new JNKAi <Components/JNKAi.cellml>`_.
- The :math:`K^{+}` efflux through the voltage-operated :math:`K^{+}` channels (KC): reuse the component `JKi <SinglePASMC/Components/JKi.cellml>`_ that has the same definition.
- The flux via the :math:`Cl^{-}` channels: while the `JCli <SinglePASMC/Components/JCli.cellml>`_ in the `Gosak, Marko, et al (2014)`_ model is the same but with a constant reversal potential :math:`v_{Cl}`, a `new JCli <Components/JCli.cellml>`_ is defined to incorporate the Nernst equation for :math:`v_{Cl}`.
- Intracellular Ca2+ handling, including:
- The SR uptake :math:`J_{SRuptakei}`: reuse the component `JSERCAi <SinglePASMC/Components/JSERCAi.cellml>`_ that has the same definition.
- Calcium Induced Calcium Release (CICR) via the ryanodine receptors: reuse the component `JCICRi <SinglePASMC/Components/JCICRi.cellml>`_ that has the same definition.
- Basal Ca2+ leak: reuse the component `Jleaki <SinglePASMC/Components/Jleaki.cellml>`_ that has the same definition.
- The flux related to the :math:`IP_{3}` concentration: a new component defined in `JIP3i <Components/JIP3i.cellml>`_ .
- The flux related to the :math:`PLC-\delta`: a new component defined in `JPLCdeltai <Components/JPLCdeltai.cellml>`_ .
- The flux due to :math:`IP_{3}` degradation: a new component defined in `Jdegradi <Components/Jdegradi.cellml>`_ .
- :math:`Ca^{2+}` concentration in the cytosol (c): since the `Cai <SinglePASMC/Components/Cai.cellml>`_ definition in the `Gosak, Marko, et al (2014)`_ model does not incorporate :math:`J_{IP3i}`, this component in the `Koenigsberger, Michèle, et al. (2004)`_ model is newly defined in `new Cai <Components/Cai.cellml>`_, which also reflects the differences of the fluxes direction definition mentioned above.
- :math:`Ca^{2+}` concentration in sarcoplasmic reticulum (s): reuse the component `Casr <SinglePASMC/Components/Casr.cellml>`_ that has the same definition.
- The dynamics of the cell membrane potential (v): reuse the component `Vm <SinglePASMC/Components/Vm.cellml>`_ that has the same definition, while the differences of the fluxes direction definition mentioned above are already incorporated.
- :math:`IP_{3}` concentration in the cell (I): a new component defined in `IP3 <Components/IP3.cellml>`_
Each of these blocks is itself a CellML model, which enables us to reuse the various components in future studies and models.
Experiments
---------------------
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 experiment <Experiments/SMC_KCl_noise.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 ``plotFig2_1.py``, ``plotFig2_2.py``, and ``plotFig3.py`` are ready to plot the figures in the `Single-cell response experiment <Experiments/SMC_KCl_noise.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.
.. figure:: Doc/Table1.png
:width: 85%
:align: center
:alt: Parameters
2. The Fig 3 matches the original data well, while the simulation result of Fig 2 is not exactly align with the original data, which could be caused by the parameter settings in Table 1 and the stochastic nature of the simulation settings.
.. _OpenCOR: https://opencor.ws/
