Location: FCU_ExcitationContraction_Coupling @ b2b0684096cb / exposure / exposure_frontpage.rst

Shelley Fong <sfon036@UoA.auckland.ac.nz>
2022-07-11 10:39:00+12:00
Merge remote-tracking branch 'main/master'
Permanent Source URI:

About this Functional Cell Unit

This model is a Functional Cell Unit of calcium handling within a skeletal muscle cell, leading excitation-contraction coupling.

This is a composite module, composed of several individual modules, and merged together in a modular fashion.

        - Stimulus current or action potential.
		- Velocity of sarcomere stretching.
        - Tension generated by sarcomere.
Model status

The current CellML implementation compiles in OpenCOR.

Model overview
All components are presented in `bond-graph` form.
Components are made by converting an existing kinetic model and translating into bond-graph form. 

.. figure:: exposure/FCU_BG_picture.png
   :width: 100%
   :align: center
   :alt: Components of the model

   Components of the model. The system is divided into four compartments: the cytosol (i), the exterior (o), the sarcoplasmic reticulum (SR) and the diadic space (D). The crossbridge (XB) exists within the cytosol. As indicated in bold, each compartment has its own set of unique ionic species.
A description of the process to find bond-graph parameter is shown in the folder `parameter_finder <parameter_finder>`_, which relies on the:

1. stoichiometry of system

2. kinetic constants for forward/reverse reactions

  - If not already, all reactions are made reversible by assigning a small value to the reverse  direction.
3. `linear algebra script <https://models.physiomeproject.org/workspace/7a8/rawfile/4ae281c45fbbd7c0a2be6c86eb946a84c35f0f70/parameter_finder/find_BG_parameters_composite.py>`_, which outputs the bond-graph parameters K and :math:`{\kappa}`.

Here, this solve process is performed in Python.

Modular description


CellML supports importing individual modular components which comprise the FCU. These modules are then able to be re-used in other composite models.
These CellML components listed below:
.. csv-table:: Model components of this FCU, including the source of kinetic origin
   :header: "Component", "Abbreviation", "Source"
   :widths: 25, 15, 25   
   "`Calcium leak <https://models.physiomeproject.org/workspace/835>`_", "Ca_leak", "`Luo and Rudy (1994) <https://models.physiomeproject.org/e/81>`_"
   "`Crossbridge Troponin-C <https://models.physiomeproject.org/e/800>`_", "XB and TRPN-Ca", "`Niederer et al. (2006) <https://models.physiomeproject.org/exposure/97fb1de5199b1a74c89281db97aecc13>`_ , `Land et. al. (2017) <http://dx.doi.org/10.1016/j.yjmcc.2017.03.008>`_"
   "`Diadic calcium diffusion <https://models.physiomeproject.org/workspace/88c>`_", "DiadCaDiffusion", "`Greenstein and Winslow (2002) <https://doi.org/10.1016%2FS0006-3495(02)75301-0>`_"
   "`L-type calcium channel <https://models.physiomeproject.org/workspace/6d7>`_", "LCC", "`Luo and Rudy (1994) <https://models.physiomeproject.org/e/81>`_"
   "`Sodium-calcium exchanger <https://models.physiomeproject.org/workspace/828>`_", "NCX", "`Luo and Rudy (1994) <https://models.physiomeproject.org/e/81>`_"
   "`Sarcolemmal calcium pump <https://models.physiomeproject.org/workspace/833>`_", "pCa", "`Clancy and Rudy (2001) <https://models.physiomeproject.org/e/514>`_"
   "`Phospholamban regulation <https://models.physiomeproject.org/workspace/6d1>`_", "PLB", "`Saucerman et al. (2003) <https://models.physiomeproject.org/exposure/9766d9bd0325c31e47a31b291e26ccad>`_"
   "`Ryanodine receptor <https://models.physiomeproject.org/workspace/6e3>`_", "RyR", "`Stern et al. (1999) <https://models.physiomeproject.org/exposure/b060fdbcfae8c7d85e595c24d36ab11b>`_"
   "`Sarcoplasmic/endoplasmic Ca2+ ATPase <https://models.physiomeproject.org/workspace/7a5>`_", "SERCA", "`Tran et al. (2009) <https://models.physiomeproject.org/exposure/815f3cb51960e9c9855e66996c1d1a4c>`_"
Each of these blocks is itself a CellML model, complete with bond-graph parameters appropriate for the isolated system.