Location: BG_B1AR @ 8853e4bdc7cf / exposure / exposure_frontpage.rst

Author:
Shelley Fong <s.fong@auckland.ac.nz>
Date:
2021-11-17 16:02:39+13:00
Desc:
fixing rst formatting
Permanent Source URI:
https://models.cellml.org/workspace/6ba/rawfile/8853e4bdc7cfbd5660c9a4fa70314ab5b87e9db0/exposure/exposure_frontpage.rst

About this model
====================

This is a bond graph model of beta-1 adrenergic receptor ( :math:`{\beta}` 1AR) metabolism in the cardiac cell.

    **INPUTS:** 
        - Ligand (L) stimulus e.g. isoproterenol 
        
    **OUTPUTS:** 
        - Change in molar amount of :math:`{\beta}` 1AR (R), 
        
    **REACTIONS:** 
        - Phosphorylation of :math:`{\beta}` 1AR by :math:`{\beta}` ARK
        - Phosphorylation of :math:`{\beta}` 1AR by PKACI
        

Model status
=============

The current CellML implementation runs in OpenCOR.


Model overview
===================
This model is made by from an existing kinetic model, and translating the mathematics into the bond-graph formalism. 

The creation of LR and LRG species are not included in this module. See *link to LRGbinding* for these.

.. figure:: exposure/kinetic_reactions.png
   :width: 100%
   :align: center
   :alt: Original kinetic formulations

   Original kinetic formulations.



.. figure:: exposure/BG_BARK_reaction.png
   :width: 75%
   :align: center
   :alt: BG BARK reaction
   
   Bond graph formulation of the reaction involving  the :math:`{\beta}` ARK enzyme, in the phosphorylation of :math:`{\beta}` 1AR.



.. figure:: exposure/BG_PKACI_reaction.png
   :width: 75%
   :align: center
   :alt: BG PKACI reaction
   
   Bond graph formulation of the reaction involving the PKACI enzyme, in the phosphorylation of :math:`{\beta}` 1AR at another site to the :math:`{\beta}`ARK enzyme.



Parameter finding
~~~~~~~~~~~~~~~~~
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/6ba/file/c32be022513dc4b620d74803a6ace6ca2d817e11/parameter_finder/find_BG_parameters.py>`_. 

Here, this solve process is performed in Python.


Original kinetic model
======================
Saucerman et al: `Modeling beta-adrenergic control of cardiac myocyte contractility in silico. <https://models.physiomeproject.org/exposure/9766d9bd0325c31e47a31b291e26ccad>`_