- Author:
- Geoff Nunns <gnunns1@jhu.edu>
- Date:
- 2010-05-13 15:18:39+12:00
- Desc:
- Added equation, fixed initial conditions and edited curation status.
- Permanent Source URI:
- https://models.physiomeproject.org/workspace/sneyd_dufour_2002/rawfile/5cc38bf03ed21d96afe0a92d63b3707c2c476456/sneyd_dufour_2002.cellml
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This CellML file was generated on 13/05/2010 at 3:13:21 at p.m. using:
COR (0.9.31.1371)
Copyright 2002-2010 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/
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<title>A Dynamic Model Of The Type-2 Inositol Triphosphate Receptor</title>
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This CellML model runs in OpenCell and COR and the units are consistent throughout. The model runs to recreate published results and is currently configured to recreate Figure 4 (Lower Plot, Trace 4), but variation of the IP3 and Calcium concentrations will allow the model to recreate different figures.
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ABSTRACT: The dynamic properties of the inositol (1,4,5)-trisphosphate (IP(3)) receptor are crucial for the control of intracellular Ca(2+), including the generation of Ca(2+) oscillations and waves. However, many models of this receptor do not agree with recent experimental data on the dynamic responses of the receptor. We construct a model of the IP(3) receptor and fit the model to dynamic and steady-state experimental data from type-2 IP(3) receptors. Our results indicate that, (i) Ca(2+) binds to the receptor using saturating, not mass-action, kinetics; (ii) Ca(2+) decreases the rate of IP(3) binding while simultaneously increasing the steady-state sensitivity of the receptor to IP(3); (iii) the rate of Ca(2+)-induced receptor activation increases with Ca(2+) and is faster than Ca(2+)-induced receptor inactivation; and (iv) IP(3) receptors are sequentially activated and inactivated by Ca(2+) even when IP(3) is bound. Our results emphasize that measurement of steady-state properties alone is insufficient to characterize the functional properties of the receptor.
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The original paper reference is cited below:
</para>
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A dynamic model of the type-2 inositol triphosphate receptor, James Sneyd and Jean-Francois Dufour, 2002, <emphasis>Proceedings of the National Academy of Sciences </emphasis>, 99, 2398-2403. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11842185&dopt=Abstract">PubMed ID: 11842185</ulink>
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<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci>phi_4</ci>
<ci>O</ci>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci>k_1b</ci>
<ci>l_2b</ci>
</apply>
<ci>I_2</ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>phi_4b</ci>
<ci>A</ci>
</apply>
<apply>
<times/>
<ci>phi_5</ci>
<ci>A</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="open_probability">
<variable name="open_probability" units="dimensionless"/>
<variable name="O" units="dimensionless" public_interface="in"/>
<variable name="A" units="dimensionless" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>open_probability</ci>
<apply>
<power/>
<apply>
<plus/>
<apply>
<times/>
<cn cellml:units="dimensionless">0.1</cn>
<ci>O</ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless">0.9</cn>
<ci>A</ci>
</apply>
</apply>
<cn cellml:units="dimensionless">4</cn>
</apply>
</apply>
</math>
</component>
<component xmlns="http://www.cellml.org/cellml/1.0#" name="reaction_rate_constants">
<variable name="phi_1" units="first_order_rate_constant" public_interface="out"/>
<variable name="phi_2" units="second_order_rate_constant" public_interface="out"/>
<variable name="phi_2b" units="first_order_rate_constant" public_interface="out"/>
<variable name="phi_3" units="second_order_rate_constant" public_interface="out"/>
<variable name="phi_4" units="first_order_rate_constant" public_interface="out"/>
<variable name="phi_4b" units="first_order_rate_constant" public_interface="out"/>
<variable name="phi_5" units="first_order_rate_constant" public_interface="out"/>
<variable name="k_1a" units="second_order_rate_constant" initial_value="0.64"/>
<variable name="k_1b" units="first_order_rate_constant" initial_value="0.04" public_interface="out"/>
<variable name="k_2a" units="second_order_rate_constant" initial_value="37.4"/>
<variable name="k_2b" units="first_order_rate_constant" initial_value="1.4"/>
<variable name="k_3a" units="second_order_rate_constant" initial_value="0.11"/>
<variable name="k_3b" units="first_order_rate_constant" initial_value="29.8" public_interface="out"/>
<variable name="k_4a" units="second_order_rate_constant" initial_value="4"/>
<variable name="k_4b" units="first_order_rate_constant" initial_value="0.54"/>
<variable name="l_2a" units="first_order_rate_constant" initial_value="1.7"/>
<variable name="l_2b" units="first_order_rate_constant" initial_value="0.8" public_interface="out"/>
<variable name="l_4a" units="second_order_rate_constant" initial_value="1.7"/>
<variable name="l_4b" units="second_order_rate_constant" initial_value="2.5"/>
<variable name="l_6a" units="first_order_rate_constant" initial_value="4707"/>
<variable name="l_6b" units="first_order_rate_constant" initial_value="11.4"/>
<variable name="L_1" units="micromolar" initial_value="0.12"/>
<variable name="L_3" units="micromolar" initial_value="0.025"/>
<variable name="L_5" units="micromolar" initial_value="54.7"/>
<variable name="p" units="micromolar" initial_value="10" public_interface="out"/>
<variable name="c" units="micromolar" initial_value="1"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>phi_1</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<plus/>
<apply>
<times/>
<ci>k_1a</ci>
<ci>L_1</ci>
</apply>
<ci>l_2a</ci>
</apply>
<ci>c</ci>
</apply>
<apply>
<plus/>
<ci>L_1</ci>
<apply>
<times/>
<ci>c</ci>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>L_1</ci>
<ci>L_3</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>phi_2</ci>
<apply>
<divide/>
<apply>
<plus/>
<apply>
<times/>
<ci>k_2a</ci>
<ci>L_3</ci>
</apply>
<apply>
<times/>
<ci>l_4a</ci>
<ci>c</ci>
</apply>
</apply>
<apply>
<plus/>
<ci>L_3</ci>
<apply>
<times/>
<ci>c</ci>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>L_3</ci>
<ci>L_1</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>phi_2b</ci>
<apply>
<divide/>
<apply>
<plus/>
<ci>k_2b</ci>
<apply>
<times/>
<ci>l_4b</ci>
<ci>c</ci>
</apply>
</apply>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>c</ci>
<ci>L_5</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>phi_3</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>k_3a</ci>
<ci>L_5</ci>
</apply>
<apply>
<plus/>
<ci>c</ci>
<ci>L_5</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>phi_4</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<plus/>
<apply>
<times/>
<ci>k_4a</ci>
<ci>L_5</ci>
</apply>
<ci>l_6a</ci>
</apply>
<ci>c</ci>
</apply>
<apply>
<plus/>
<ci>c</ci>
<ci>L_5</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>phi_4b</ci>
<apply>
<divide/>
<apply>
<times/>
<ci>L_1</ci>
<apply>
<plus/>
<ci>k_4b</ci>
<ci>l_6b</ci>
</apply>
</apply>
<apply>
<plus/>
<ci>c</ci>
<ci>L_1</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>phi_5</ci>
<apply>
<divide/>
<apply>
<times/>
<apply>
<plus/>
<apply>
<times/>
<ci>k_1a</ci>
<ci>L_1</ci>
</apply>
<ci>l_2a</ci>
</apply>
<ci>c</ci>
</apply>
<apply>
<plus/>
<ci>c</ci>
<ci>L_1</ci>
</apply>
</apply>
</apply>
</math>
</component>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="open_probability" component_2="O"/>
<map_variables variable_1="O" variable_2="O"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="open_probability" component_2="A"/>
<map_variables variable_1="A" variable_2="A"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="R" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="O" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="I_1" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="I_2" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="A" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="R" component_2="reaction_rate_constants"/>
<map_variables variable_1="phi_1" variable_2="phi_1"/>
<map_variables variable_1="phi_2" variable_2="phi_2"/>
<map_variables variable_1="phi_2b" variable_2="phi_2b"/>
<map_variables variable_1="k_1b" variable_2="k_1b"/>
<map_variables variable_1="l_2b" variable_2="l_2b"/>
<map_variables variable_1="p" variable_2="p"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="O" component_2="reaction_rate_constants"/>
<map_variables variable_1="phi_3" variable_2="phi_3"/>
<map_variables variable_1="phi_2" variable_2="phi_2"/>
<map_variables variable_1="phi_2b" variable_2="phi_2b"/>
<map_variables variable_1="phi_4" variable_2="phi_4"/>
<map_variables variable_1="phi_4b" variable_2="phi_4b"/>
<map_variables variable_1="k_3b" variable_2="k_3b"/>
<map_variables variable_1="p" variable_2="p"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="I_1" component_2="reaction_rate_constants"/>
<map_variables variable_1="phi_1" variable_2="phi_1"/>
<map_variables variable_1="k_1b" variable_2="k_1b"/>
<map_variables variable_1="l_2b" variable_2="l_2b"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="I_2" component_2="reaction_rate_constants"/>
<map_variables variable_1="phi_5" variable_2="phi_5"/>
<map_variables variable_1="k_1b" variable_2="k_1b"/>
<map_variables variable_1="l_2b" variable_2="l_2b"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="A" component_2="reaction_rate_constants"/>
<map_variables variable_1="phi_5" variable_2="phi_5"/>
<map_variables variable_1="phi_4" variable_2="phi_4"/>
<map_variables variable_1="phi_4b" variable_2="phi_4b"/>
<map_variables variable_1="k_1b" variable_2="k_1b"/>
<map_variables variable_1="l_2b" variable_2="l_2b"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="R" component_2="I_1"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="I_1" variable_2="I_1"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="R" component_2="O"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="O" variable_2="O"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="S" component_2="O"/>
<map_variables variable_1="S" variable_2="S"/>
<map_variables variable_1="O" variable_2="O"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="A" component_2="O"/>
<map_variables variable_1="A" variable_2="A"/>
<map_variables variable_1="O" variable_2="O"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="A" component_2="I_2"/>
<map_variables variable_1="A" variable_2="A"/>
<map_variables variable_1="I_2" variable_2="I_2"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="S" component_2="R"/>
<map_variables variable_1="R" variable_2="R"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="S" component_2="A"/>
<map_variables variable_1="A" variable_2="A"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="S" component_2="I_1"/>
<map_variables variable_1="I_1" variable_2="I_1"/>
</connection>
<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="S" component_2="I_2"/>
<map_variables variable_1="I_2" variable_2="I_2"/>
</connection>
</model>
