Location: Shear-induced nitric oxide production by endothelial cells @ d5fac872a590 / Main_Endothelial_Cell_Model.cellml
- Author:
- Fariba <fbir042@aucklanduni.ac.nz>
- Date:
- 2023-10-05 13:21:40+13:00
- Desc:
- Endothelial_Cell_Model
- Permanent Source URI:
- https://models.fieldml.org/workspace/b34/rawfile/d5fac872a590c28ecb66b07757cf5b1cd2ab6956/Main_Endothelial_Cell_Model.cellml
<?xml version='1.0' encoding='UTF-8'?>
<model name="EC_ShearStress" xmlns="http://www.cellml.org/cellml/1.1#" xmlns:cellml="http://www.cellml.org/cellml/1.1#" xmlns:xlink="http://www.w3.org/1999/xlink">
<import xlink:href="Units_Endothelial_Cell_Model.cellml">
<units name="per_uM_per_sec" units_ref="per_uM_per_sec"/>
<units name="per_sec" units_ref="per_sec"/>
<units name="uM" units_ref="uM"/>
<units name="uM2" units_ref="uM2"/>
<units name="per_uM2" units_ref="per_uM2"/>
<units name="per_uM" units_ref="per_uM"/>
<units name="uM_per_sec" units_ref="uM_per_sec"/>
</import>
<component name="Environment">
<variable name="time" public_interface="out" units="second"/>
<variable initial_value="12" name="tau" public_interface="out" units="dimensionless"/>
</component>
<component name="Activation_of_G_proteins">
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<variable initial_value="0.017" name="k_a" units="per_sec"/>
<variable name="R_star" units="dimensionless"/>
<variable initial_value="0.33" name="Gt" units="uM"/>
<variable initial_value="0.15" name="k_d" units="per_sec"/>
<variable name="tau" public_interface="in" units="dimensionless"/>
<variable initial_value="15" name="lambda" units="dimensionless"/>
<variable initial_value="0" name="IP3" public_interface="out" units="uM"/>
<variable name="r_f" units="per_sec"/>
<variable initial_value="10" name="PIP2" units="uM"/>
<variable initial_value="0.2" name="mu1" units="per_sec"/>
<variable initial_value="8.37" name="alpha" units="per_sec"/>
<variable initial_value="0.002" name="K_cp" units="per_uM"/>
<variable initial_value="0.7937" name="M_ATP" units="dimensionless"/>
<variable initial_value="10" name="r_r" units="per_sec"/>
<variable initial_value="10" name="PIP2_t" units="uM"/>
<variable name="k_PIP2_positive" public_interface="in" units="per_sec"/>
<variable initial_value="0.7024" name="k_PIP2_negative" units="per_sec"/>
<variable initial_value="0.116" name="PIP3" public_interface="out" units="uM"/>
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<diff/>
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<ci>time</ci>
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<times/>
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<minus/>
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<times/>
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<minus/>
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<times/>
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<times/>
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<eq/>
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<times/>
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<eq/>
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<times/>
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<times/>
<ci>r_r</ci>
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<times/>
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<minus/>
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<times/>
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</apply>
</math>
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<component name="Calcium_signalling">
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<variable initial_value="1e-07" name="k_leak" units="per_uM_per_sec"/>
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<variable initial_value="6.64" name="k_rel" units="per_sec"/>
<variable name="IP3" public_interface="in" units="uM"/>
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<variable initial_value="0.32" name="k_5" units="uM"/>
<variable name="q_MSIC" units="uM_per_sec"/>
<variable name="q_CCE" units="uM_per_sec"/>
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<variable name="psi" units="per_uM"/>
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<variable name="cGMP" public_interface="in" units="uM"/>
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<variable initial_value="300" name="k_off" units="per_sec"/>
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<diff/>
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<plus/>
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<minus/>
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<times/>
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<times/>
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<times/>
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<minus/>
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<plus/>
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<minus/>
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<times/>
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<power/>
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<divide/>
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<plus/>
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<divide/>
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<plus/>
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<times/>
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<root/>
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<times/>
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<power/>
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<times/>
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<plus/>
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<root/>
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<plus/>
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<times/>
<cn cellml:units="dimensionless">16</cn>
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<power/>
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<times/>
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<minus/>
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<times/>
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<eq/>
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<diff/>
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<minus/>
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<times/>
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<minus/>
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<times/>
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<variable name="tau" public_interface="in" units="dimensionless"/>
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<variable initial_value="0.003" name="eta" units="per_sec"/>
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<variable initial_value="0.021" name="k_1p" units="per_sec"/>
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<variable initial_value="1" name="AKT_tot" public_interface="out" units="uM"/>
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<variable name="k_AKT_positive" units="per_sec"/>
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<plus/>
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<plus/>
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<tanh/>
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<plus/>
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<minus/>
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<times/>
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<minus/>
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<times/>
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<eq/>
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<diff/>
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<times/>
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<minus/>
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<eq/>
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<divide/>
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<times/>
<cn cellml:units="dimensionless">0.1</cn>
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<minus/>
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<eq/>
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<divide/>
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<times/>
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<minus/>
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<eq/>
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<times/>
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<eq/>
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<times/>
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</math>
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<component name="Phosphorylation_and_formation_of_eNOS_complexes">
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<variable initial_value="0.0002668" name="Ca4_CaM" units="uM"/>
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<divide/>
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<diff/>
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<divide/>
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<power/>
<apply>
<times/>
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<power/>
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<minus/>
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<plus/>
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<minus/>
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<plus/>
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</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>eNOS_CaM_star</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k_eAKT_positive</ci>
<ci>eNOS_CaM</ci>
</apply>
<apply>
<times/>
<ci>k_eAKT_negative</ci>
<ci>eNOS_CaM_star</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>k_eAKT_positive</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>k_eAKT_max</ci>
<ci>AKT_star</ci>
</apply>
<ci>AKT_tot</ci>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>eNOS_Cav_0</ci>
</apply>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<ci>k_Thr_positive</ci>
<ci>PKC_star</ci>
<ci>eNOS_Cav</ci>
</apply>
<ci>PKC_tot</ci>
</apply>
<apply>
<times/>
<ci>k_Thr_negative</ci>
<ci>eNOS_Cav_0</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="NO_production">
<variable name="time" public_interface="in" units="second"/>
<variable initial_value="0.0089" name="NO" units="uM"/>
<variable initial_value="382" name="lambda_NO" units="per_sec"/>
<variable name="Q_NO" units="uM_per_sec"/>
<variable initial_value="5" name="O2" units="uM"/>
<variable initial_value="23.2" name="k_mNO" units="uM"/>
<variable name="eNOS_CaM" public_interface="in" units="uM"/>
<variable name="eNOS_CaM_star" public_interface="in" units="uM"/>
<variable initial_value="9" name="Phi" units="dimensionless"/>
<variable name="Q_sGC" units="uM_per_sec"/>
<variable initial_value="0.1" name="sGC" units="uM"/>
<variable initial_value="0.022" name="R_NO_max" units="per_sec"/>
<variable initial_value="0.00120016" name="a_0" units="uM2"/>
<variable initial_value="0.03733" name="a_1" units="uM"/>
<variable initial_value="3.8624" name="cGMP" public_interface="out" units="uM"/>
<variable initial_value="1.26" name="v_cGMP_max" units="uM_per_sec"/>
<variable initial_value="4.8e-06" name="g_0" units="uM2"/>
<variable initial_value="0.03533" name="g_1" units="uM"/>
<variable initial_value="0.0695" name="X" units="per_sec"/>
<variable initial_value="2" name="k_cGMP" units="uM"/>
<variable initial_value="300" name="r" units="per_sec"/>
<variable initial_value="1" name="b_0" units="dimensionless"/>
<variable initial_value="0.01515" name="b_1" units="uM"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>Q_NO</ci>
<apply>
<times/>
<ci>r</ci>
<apply>
<plus/>
<ci>eNOS_CaM</ci>
<apply>
<times/>
<ci>Phi</ci>
<ci>eNOS_CaM_star</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>Q_sGC</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>R_NO_max</ci>
<ci>sGC</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>b_1</ci>
<ci>NO</ci>
</apply>
<apply>
<times/>
<ci>b_0</ci>
<apply>
<power/>
<ci>NO</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<plus/>
<ci>a_0</ci>
<apply>
<times/>
<ci>a_1</ci>
<ci>NO</ci>
</apply>
<apply>
<power/>
<ci>NO</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>NO</ci>
</apply>
<apply>
<minus/>
<apply>
<minus/>
<ci>Q_NO</ci>
<ci>Q_sGC</ci>
</apply>
<apply>
<times/>
<ci>lambda_NO</ci>
<ci>NO</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>cGMP</ci>
</apply>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<ci>v_cGMP_max</ci>
<apply>
<plus/>
<ci>g_0</ci>
<apply>
<times/>
<ci>g_1</ci>
<ci>NO</ci>
</apply>
<apply>
<power/>
<ci>NO</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
<apply>
<plus/>
<ci>a_0</ci>
<apply>
<times/>
<ci>a_1</ci>
<ci>NO</ci>
</apply>
<apply>
<power/>
<ci>NO</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>X</ci>
<apply>
<power/>
<ci>cGMP</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
<apply>
<plus/>
<ci>k_cGMP</ci>
<ci>cGMP</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<connection>
<map_components component_1="Environment" component_2="Activation_of_G_proteins"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="tau" variable_2="tau"/>
</connection>
<connection>
<map_components component_1="Environment" component_2="Calcium_signalling"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="tau" variable_2="tau"/>
</connection>
<connection>
<map_components component_1="Environment" component_2="Activation_of_protein_kinases"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="tau" variable_2="tau"/>
</connection>
<connection>
<map_components component_1="Environment" component_2="Phosphorylation_and_formation_of_eNOS_complexes"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Environment" component_2="NO_production"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Activation_of_G_proteins" component_2="Calcium_signalling"/>
<map_variables variable_1="IP3" variable_2="IP3"/>
</connection>
<connection>
<map_components component_1="NO_production" component_2="Calcium_signalling"/>
<map_variables variable_1="cGMP" variable_2="cGMP"/>
</connection>
<connection>
<map_components component_1="Activation_of_G_proteins" component_2="Activation_of_protein_kinases"/>
<map_variables variable_1="k_PIP2_positive" variable_2="k_PIP2_positive"/>
<map_variables variable_1="PIP3" variable_2="PIP3"/>
</connection>
<connection>
<map_components component_1="Phosphorylation_and_formation_of_eNOS_complexes" component_2="NO_production"/>
<map_variables variable_1="eNOS_CaM" variable_2="eNOS_CaM"/>
<map_variables variable_1="eNOS_CaM_star" variable_2="eNOS_CaM_star"/>
</connection>
<connection>
<map_components component_1="Phosphorylation_and_formation_of_eNOS_complexes" component_2="Calcium_signalling"/>
<map_variables variable_1="Ca2_c" variable_2="Ca2_c"/>
</connection>
<connection>
<map_components component_1="Phosphorylation_and_formation_of_eNOS_complexes" component_2="Activation_of_protein_kinases"/>
<map_variables variable_1="AKT_star" variable_2="AKT_star"/>
<map_variables variable_1="AKT_tot" variable_2="AKT_tot"/>
<map_variables variable_1="PKC_tot" variable_2="PKC_tot"/>
<map_variables variable_1="PKC_star" variable_2="PKC_star"/>
</connection>
</model>