- Author:
- Wei Liu <devnull@localhost>
- Date:
- 2009-09-17 15:51:20+12:00
- Desc:
- Original Model
- Permanent Source URI:
- https://models.cellml.org/workspace/lemon_gibson_bennett_2003/rawfile/dc3cd6c49a1a568dd1f9fc961282a8bd8ae52238/Gibson_s_Model.cellml
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<!--
This CellML file was generated on 21/08/2009 at 9:19:39 at a.m. using:
COR (0.9.31.1309)
Copyright 2002-2009 Dr Alan Garny
http://cor.physiol.ox.ac.uk/ - cor@physiol.ox.ac.uk
CellML 1.0 was used to generate this model
http://www.cellml.org/
-->
<model xml:base="file:///F:/Project/Models/ORIGINAL_ALL.cellml" name="Gibson_Lemon_Model" cmeta:id="Gibson_Lemon_Model" xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<section id="sec_status">
<title>Model Status</title>
<para>
This CellML model is the model which was used to produce the original results in the paper. The units have been checked and are consistent and this model is known to be valid CellML.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
The Gibson's Model can be generally divided into 3 stages, The regulation of metabotropic receptor activitity, the G-Protein cascade and the Calcium Dynamics in the cytosol.
</para>
<para></para>
<para>
Regulation of Metabotropic Receptor Activity is the inital step of the Calcium Signalling Pathway.
</para>
<para>
Internalization of the uridine triphosphate (UTP) binding P2Y2 receptor in the cell surface activates the G-Protein Cascade Pathway. Phosphorylation of both binding and unbound P2Y2 receptors uncouple them from G-Proteins, thus deactivates the G-Protein Cascade Pathway. The internalization of the phosphorylated P2Y2 receptors leads to dephosphorylation and recycle of the P2Y2 receptor to cell surface.
</para>
<para></para>
<para>
G-Protein Cascade is the pathways that induced by the P2Y2 receptor activity and it hydrolysis phosphatidylinositol 4,5-bisphosphate (PIP2) to produce inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) (ratio PIP2:IP3:DAG = 1:1:1).
</para>
<para>
First of all, the activated G-Protein binds with phospholipase C (PLC) in the cytosol, and after the binding of a Ca2+ ion on the complex, PLC is fully activated to hydrolyse PIP2 in the cytosol producing IP3 and DAG.
</para>
<para></para>
<para>
Calcium Dynamics
</para>
<para>
Once IP3 is produced in the cell, it binds with the IP3 receptor on the ER surface and induces the Calcium flow from ER to cytosol. And the Calcium Concentration in cytosol, is both dependent on the cytosolic calcium concentration and ER calcium concentration.
</para>
<para>
This model of the calcium oscillation in lung mechanotransduction is based on the original paper cited below:
</para>
<para>
Metabotropic receptoractivation, desensitization and sequestration � I: modelling calcium and inositol 1,4,5-trisphosphate dynamics following receptor activation. G.Lemon, W.G. Gibson, M.R. Bennett, 2003, Journal of Theoretical Biology, 223, 93-111. <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/12782119">PubMed ID: 12782119</ulink>
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>Diagram of model</title>
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<imagedata fileref="Gibson_s_Model.png"/>
</imageobject>
</mediaobject>
<caption>A schematic diagram of the calcium oscillation pathway induced by physcial force described by the mathematical model.</caption>
</informalfigure>
</sect1>
</article>
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<ci>K_x</ci>
<ci>B_x</ci>
</apply>
<apply>
<power/>
<apply>
<plus/>
<ci>K_x</ci>
<ci>C</ci>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
</math>
</component>
<component name="gamma">
<variable name="gamma" units="dimensionless" public_interface="out"/>
<variable name="K_e" units="micromolar" public_interface="in"/>
<variable name="B_e" units="micromolar" public_interface="in"/>
<variable name="K_x" units="micromolar" public_interface="in"/>
<variable name="B_x" units="micromolar" public_interface="in"/>
<variable name="C" units="micromolar" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>gamma</ci>
<apply>
<power/>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>B_e</ci>
<apply>
<plus/>
<ci>K_e</ci>
<ci>C</ci>
</apply>
</apply>
<apply>
<divide/>
<ci>B_x</ci>
<apply>
<plus/>
<ci>K_x</ci>
<ci>C</ci>
</apply>
</apply>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</apply>
</math>
</component>
<component name="C_ER">
<variable name="C_ER" units="micromolar" public_interface="out"/>
<variable name="K_ER" units="micromolar" public_interface="in"/>
<variable name="B_ER" units="micromolar" public_interface="in"/>
<variable name="epsilon_r" units="dimensionless" public_interface="in"/>
<variable name="C_T" units="micromolar" public_interface="in"/>
<variable name="C" units="micromolar" public_interface="in"/>
<variable name="gamma" units="dimensionless" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>C_ER</ci>
<apply>
<times/>
<apply>
<divide/>
<ci>K_ER</ci>
<apply>
<times/>
<ci>B_ER</ci>
<ci>epsilon_r</ci>
</apply>
</apply>
<apply>
<minus/>
<ci>C_T</ci>
<apply>
<divide/>
<ci>C</ci>
<ci>gamma</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="RS_E">
<variable name="RS_E" units="dimensionless" public_interface="out"/>
<variable name="R_T" units="dimensionless" public_interface="in"/>
<variable name="L" units="micromolar" public_interface="in"/>
<variable name="K_1" units="micromolar" public_interface="in"/>
<variable name="K_2" units="micromolar" public_interface="in"/>
<variable name="k_r" units="per_second" public_interface="in"/>
<variable name="k_p" units="per_second" public_interface="in"/>
<variable name="k_e" units="per_second" public_interface="in"/>
<variable name="xi" units="dimensionless" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>RS_E</ci>
<apply>
<plus/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>k_r</ci>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<ci>k_p</ci>
<ci>k_e</ci>
</apply>
<apply>
<plus/>
<ci>K_2</ci>
<ci>L</ci>
</apply>
</apply>
<apply>
<plus/>
<ci>K_1</ci>
<ci>L</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<ci>k_r</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>k_p</ci>
<ci>L</ci>
</apply>
<apply>
<plus/>
<ci>K_1</ci>
<ci>L</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<apply>
<divide/>
<apply>
<times/>
<ci>k_r</ci>
<ci>k_p</ci>
</apply>
<ci>k_e</ci>
</apply>
<apply>
<plus/>
<ci>K_2</ci>
<ci>L</ci>
</apply>
</apply>
<apply>
<plus/>
<ci>K_1</ci>
<ci>L</ci>
</apply>
</apply>
</apply>
</apply>
<ci>xi</ci>
<ci>R_T</ci>
</apply>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>xi</ci>
</apply>
<ci>R_T</ci>
</apply>
</apply>
</apply>
</math>
</component>
<connection>
<map_components component_1="RS" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="RS_p" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="environment" component_2="G_GTP"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="environment" component_2="IP_3"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="environment" component_2="PIP_2"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="environment" component_2="C"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="h" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="RS" component_2="ligand"/>
<map_variables variable_1="L" variable_2="L"/>
</connection>
<connection>
<map_components component_1="RS_p" component_2="ligand"/>
<map_variables variable_1="L" variable_2="L"/>
</connection>
<connection>
<map_components component_1="rho_r" component_2="ligand"/>
<map_variables variable_1="L" variable_2="L"/>
</connection>
<connection>
<map_components component_1="RS" component_2="Parameters"/>
<map_variables variable_1="R_T" variable_2="R_T"/>
<map_variables variable_1="K_1" variable_2="K_1"/>
<map_variables variable_1="k_r" variable_2="k_r"/>
<map_variables variable_1="k_p" variable_2="k_p"/>
</connection>
<connection>
<map_components component_1="RS" component_2="rho_r"/>
<map_variables variable_1="RS" variable_2="RS"/>
</connection>
<connection>
<map_components component_1="RS_p" component_2="Parameters"/>
<map_variables variable_1="R_T" variable_2="R_T"/>
<map_variables variable_1="K_1" variable_2="K_1"/>
<map_variables variable_1="K_2" variable_2="K_2"/>
<map_variables variable_1="k_r" variable_2="k_r"/>
<map_variables variable_1="k_p" variable_2="k_p"/>
<map_variables variable_1="k_e" variable_2="k_e"/>
</connection>
<connection>
<map_components component_1="RS" component_2="RS_p"/>
<map_variables variable_1="RS" variable_2="RS"/>
<map_variables variable_1="RS_p" variable_2="RS_p"/>
</connection>
<connection>
<map_components component_1="G_GTP" component_2="rho_r"/>
<map_variables variable_1="rho_r" variable_2="rho_r"/>
</connection>
<connection>
<map_components component_1="G_GTP" component_2="Parameters"/>
<map_variables variable_1="G_T" variable_2="G_T"/>
<map_variables variable_1="delta" variable_2="delta"/>
<map_variables variable_1="k_a" variable_2="k_a"/>
<map_variables variable_1="k_d" variable_2="k_d"/>
</connection>
<connection>
<map_components component_1="IP_3" component_2="PIP_2"/>
<map_variables variable_1="IP_3" variable_2="IP_3"/>
<map_variables variable_1="PIP_2" variable_2="PIP_2"/>
</connection>
<connection>
<map_components component_1="IP_3" component_2="r_h"/>
<map_variables variable_1="r_h" variable_2="r_h"/>
</connection>
<connection>
<map_components component_1="IP_3" component_2="Parameters"/>
<map_variables variable_1="k_deg" variable_2="k_deg"/>
<map_variables variable_1="N_a" variable_2="N_a"/>
<map_variables variable_1="v" variable_2="v"/>
</connection>
<connection>
<map_components component_1="PIP_2" component_2="r_h"/>
<map_variables variable_1="r_h" variable_2="r_h"/>
</connection>
<connection>
<map_components component_1="PIP_2" component_2="Parameters"/>
<map_variables variable_1="r_r" variable_2="r_r"/>
<map_variables variable_1="PIP_2_T" variable_2="PIP_2_T"/>
<map_variables variable_1="k_deg" variable_2="k_deg"/>
<map_variables variable_1="N_a" variable_2="N_a"/>
<map_variables variable_1="v" variable_2="v"/>
</connection>
<connection>
<map_components component_1="G_GTP" component_2="r_h"/>
<map_variables variable_1="G" variable_2="G"/>
</connection>
<connection>
<map_components component_1="r_h" component_2="Parameters"/>
<map_variables variable_1="alpha" variable_2="alpha"/>
<map_variables variable_1="K_c" variable_2="K_c"/>
</connection>
<connection>
<map_components component_1="rho_r" component_2="Parameters"/>
<map_variables variable_1="R_T" variable_2="R_T"/>
<map_variables variable_1="K_1" variable_2="K_1"/>
<map_variables variable_1="xi" variable_2="xi"/>
</connection>
<connection>
<map_components component_1="C" component_2="r_h"/>
<map_variables variable_1="C" variable_2="C"/>
</connection>
<connection>
<map_components component_1="C" component_2="Parameters"/>
<map_variables variable_1="epsilon_r" variable_2="epsilon_r"/>
<map_variables variable_1="eta_1" variable_2="eta_1"/>
<map_variables variable_1="eta_2" variable_2="eta_2"/>
<map_variables variable_1="eta_3" variable_2="eta_3"/>
<map_variables variable_1="k_3" variable_2="k_3"/>
</connection>
<connection>
<map_components component_1="C" component_2="h"/>
<map_variables variable_1="h" variable_2="h"/>
</connection>
<connection>
<map_components component_1="C" component_2="tau_h"/>
<map_variables variable_1="C" variable_2="C"/>
</connection>
<connection>
<map_components component_1="C" component_2="h_infinit"/>
<map_variables variable_1="C" variable_2="C"/>
</connection>
<connection>
<map_components component_1="C" component_2="m_infinit"/>
<map_variables variable_1="m_infinit" variable_2="m_infinit"/>
<map_variables variable_1="C" variable_2="C"/>
</connection>
<connection>
<map_components component_1="C" component_2="beta"/>
<map_variables variable_1="beta" variable_2="beta"/>
<map_variables variable_1="C" variable_2="C"/>
</connection>
<connection>
<map_components component_1="C" component_2="C_ER"/>
<map_variables variable_1="C_ER" variable_2="C_ER"/>
<map_variables variable_1="C" variable_2="C"/>
</connection>
<connection>
<map_components component_1="h" component_2="h_infinit"/>
<map_variables variable_1="h_infinit" variable_2="h_infinit"/>
</connection>
<connection>
<map_components component_1="h" component_2="tau_h"/>
<map_variables variable_1="tau_h" variable_2="tau_h"/>
</connection>
<connection>
<map_components component_1="tau_h" component_2="Parameters"/>
<map_variables variable_1="a_2" variable_2="a_2"/>
</connection>
<connection>
<map_components component_1="tau_h" component_2="zeta"/>
<map_variables variable_1="zeta" variable_2="zeta"/>
</connection>
<connection>
<map_components component_1="h_infinit" component_2="zeta"/>
<map_variables variable_1="zeta" variable_2="zeta"/>
</connection>
<connection>
<map_components component_1="zeta" component_2="Parameters"/>
<map_variables variable_1="d_1" variable_2="d_1"/>
<map_variables variable_1="d_2" variable_2="d_2"/>
<map_variables variable_1="d_3" variable_2="d_3"/>
</connection>
<connection>
<map_components component_1="zeta" component_2="IP_3"/>
<map_variables variable_1="IP_3" variable_2="IP_3"/>
</connection>
<connection>
<map_components component_1="m_infinit" component_2="Parameters"/>
<map_variables variable_1="d_1" variable_2="d_1"/>
<map_variables variable_1="d_5" variable_2="d_5"/>
</connection>
<connection>
<map_components component_1="m_infinit" component_2="IP_3"/>
<map_variables variable_1="IP_3" variable_2="IP_3"/>
</connection>
<connection>
<map_components component_1="beta" component_2="Parameters"/>
<map_variables variable_1="K_e" variable_2="K_e"/>
<map_variables variable_1="K_x" variable_2="K_x"/>
<map_variables variable_1="B_e" variable_2="B_e"/>
<map_variables variable_1="B_x" variable_2="B_x"/>
</connection>
<connection>
<map_components component_1="gamma" component_2="Parameters"/>
<map_variables variable_1="K_e" variable_2="K_e"/>
<map_variables variable_1="K_x" variable_2="K_x"/>
<map_variables variable_1="B_e" variable_2="B_e"/>
<map_variables variable_1="B_x" variable_2="B_x"/>
</connection>
<connection>
<map_components component_1="gamma" component_2="C"/>
<map_variables variable_1="C" variable_2="C"/>
</connection>
<connection>
<map_components component_1="C_ER" component_2="Parameters"/>
<map_variables variable_1="K_ER" variable_2="K_ER"/>
<map_variables variable_1="B_ER" variable_2="B_ER"/>
<map_variables variable_1="epsilon_r" variable_2="epsilon_r"/>
<map_variables variable_1="C_T" variable_2="C_T"/>
</connection>
<connection>
<map_components component_1="C_ER" component_2="gamma"/>
<map_variables variable_1="gamma" variable_2="gamma"/>
</connection>
<connection>
<map_components component_1="RS_E" component_2="Parameters"/>
<map_variables variable_1="K_1" variable_2="K_1"/>
<map_variables variable_1="K_2" variable_2="K_2"/>
<map_variables variable_1="k_p" variable_2="k_p"/>
<map_variables variable_1="k_e" variable_2="k_e"/>
<map_variables variable_1="k_r" variable_2="k_r"/>
<map_variables variable_1="xi" variable_2="xi"/>
<map_variables variable_1="R_T" variable_2="R_T"/>
</connection>
<connection>
<map_components component_1="RS_E" component_2="ligand"/>
<map_variables variable_1="L" variable_2="L"/>
</connection>
</model>
