- Author:
- Mark Hanna <cipscis@gmail.com>
- Date:
- 2009-11-30 14:28:49+13:00
- Desc:
- Created 3 new models. All models run in PCEnv and COR and are able to reproduce published output. Model (a) can only produce output from figure 4 using parameters from figure 5.
- Permanent Source URI:
- https://models.physiomeproject.org/workspace/borghans_1997/rawfile/8457f8ce39ed6cece70702fcb2df4e3df909c54f/borghans_dupont_goldbeter_1997b.cellml
<?xml version='1.0' encoding='utf-8'?>
<model name="borghans_model_1997b" 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#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" cmeta:id="borghans_model_1997b">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Complex intracellular calcium oscillations. A theoretical exploration of possible mechanisms</title>
<author>
<firstname>Mark</firstname>
<surname>Hanna</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>Runs in PCEnv and COR. Reproduces published output (figures 8 and 9)</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>ABSTRACT: Intracellular Ca2+ oscillations are commonly observed in a large number of cell types in response to stimulation by an extracellular agonist. In most cell types the mechanism of regular spiking is well understood and models based on Ca2+-induced Ca2+ release (CICR) can account for many experimental observations. However, cells do not always exhibit simple Ca2+ oscillations. In response to given agonists, some cells show more complex behaviour in the form of bursting, i.e. trains of Ca2+ spikes separated by silent phases. Here we develop several theoretical models, based on physiologically plausible assumptions, that could account for complex intracellular Ca2+ oscillations. The models are all based on one- or two-pool models based on CICR. We extend these models by (i) considering the inhibition of the Ca2+-release channel on a unique intracellular store at high cytosolic Ca2+ concentrations, (ii) taking into account the Ca2+-activated degradation of inositol 1,4,5-trisphosphate (IP3), or (iii) considering explicitly the evolution of the Ca2+ concentration in two different pools, one sensitive and the other one insensitive to IP3. Besides simple periodic oscillations, these three models can all account for more complex oscillatory behaviour in the form of bursting. Moreover, the model that takes the kinetics of IP3 into account shows chaotic behaviour.</para>
<para>Complex intracellular calcium oscillations. A theoretical exploration of possible mechanisms, Jose A.M. Borghans, Genevieve Dupont, Albert Goldbeter, 1997, <emphasis>Biophysical Chemistry</emphasis>, 66, 25-41. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17029867&dopt=Abstract">PubMed ID: 17029867</ulink></para>
<informalfigure float="0" id="fig_cell_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>cell diagram</title>
</objectinfo>
<imagedata fileref="borghans_1997b.png"/>
</imageobject>
</mediaobject>
<caption>Schematic representation of the one-pool model based on CICR with Ca2+-stimulated degradation of IP3.</caption>
</informalfigure>
</sect1>
</article>
</documentation>
<!-- Units -->
<units name="min">
<!-- time: minute -->
<unit units="second" multiplier="60"/>
</units>
<units name="per_min">
<!-- per time: per minute -->
<unit units="min" exponent="-1"/>
</units>
<units name="uM">
<!-- concentration: micromolar -->
<unit units="mole" prefix="micro"/>
<unit units="litre" exponent="-1"/>
</units>
<units name="per_uM4">
<!-- "Fudge factor": micromolar^-4 -->
<unit units="uM" exponent="-4"/>
</units>
<units name="uM_per_min">
<!-- flux: micromolar per minute -->
<unit units="uM"/>
<unit units="per_min"/>
</units>
<!-- Components -->
<component name="environment">
<variable units="min" public_interface="out" name="time"/>
</component>
<component name="Ca" cmeta:id="Ca_component">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
<rdf:Description rdf:about="#Ca_component">This component stores information about Calcium ion (Ca2+) concentrations in various cellular compartments</rdf:Description>
<rdf:Description rdf:about="#Z">Ca2+ concentration in the cytosol</rdf:Description>
<rdf:Description rdf:about="#Y">Ca2+ concentration in the intracellular Ca2+ pool</rdf:Description>
</rdf:RDF>
<variable units="min" public_interface="in" private_interface="out" name="time"/>
<!-- Species -->
<variable units="uM" private_interface="out" name="Z" cmeta:id="Z" initial_value="0.1"/>
<variable units="uM" private_interface="out" name="Y" cmeta:id="Y" initial_value="1.0"/>
<!-- Flux -->
<variable units="uM_per_min" private_interface="in" name="V_in"/>
<variable units="uM_per_min" private_interface="in" name="V_2"/>
<variable units="uM_per_min" private_interface="in" name="V_3"/>
<!-- Rate constants -->
<variable units="per_min" name="K_f" initial_value="1"/>
<variable units="per_min" name="K" initial_value="10"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="Ca_maths">
<apply id="dZ/dt"><eq/>
<apply><diff/>
<bvar><ci>time</ci></bvar>
<ci>Z</ci>
</apply>
<apply><plus/>
<apply><minus/>
<ci>V_in</ci>
<ci>V_2</ci>
</apply>
<ci>V_3</ci>
<apply><minus/>
<apply><times/>
<ci>K_f</ci>
<ci>Y</ci>
</apply>
<apply><times/>
<ci>K</ci>
<ci>Z</ci>
</apply>
</apply>
</apply>
</apply>
<apply id="dY/dt"><eq/>
<apply><diff/>
<bvar><ci>time</ci></bvar>
<ci>Y</ci>
</apply>
<apply><minus/>
<apply><minus/>
<ci>V_2</ci>
<ci>V_3</ci>
</apply>
<apply><times/>
<ci>K_f</ci>
<ci>Y</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Ca_flux" cmeta:id="Ca_flux_component">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
<rdf:Description rdf:about="#Ca_flux_component">Container for Ca2+ flux-related components</rdf:Description>
<rdf:Description rdf:about="#beta">Stimulation level</rdf:Description>
</rdf:RDF>
<variable units="min" public_interface="in" private_interface="out" name="time"/>
<variable units="dimensionless" private_interface="out" name="beta" cmeta:id="beta" initial_value="0.5"/>
<variable units="uM" public_interface="in" private_interface="out" name="Z"/>
<variable units="uM" public_interface="in" private_interface="out" name="Y"/>
<variable units="uM_per_min" public_interface="out" private_interface="in" name="V_in"/>
<variable units="uM_per_min" public_interface="out" private_interface="in" name="V_2"/>
<variable units="uM_per_min" public_interface="out" private_interface="in" name="V_3"/>
</component>
<component name="V_in" cmeta:id="V_in_component">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
<rdf:Description rdf:about="#V_in_component">Component for the calculation of V_in</rdf:Description>
<rdf:Description rdf:about="#V_in">Flux of Ca2+ from the extracellular medium into the cytosol</rdf:Description>
<rdf:Description rdf:about="#v_0">Passive Ca2+ "leak" from the extracellular medium into the cytosol</rdf:Description>
<rdf:Description rdf:about="#v_1">Activated Ca2+ transport from the extracellular medium into the cytosol</rdf:Description>
</rdf:RDF>
<variable units="uM_per_min" public_interface="out" name="V_in" cmeta:id="V_in"/>
<variable units="uM_per_min" name="v_0" cmeta:id="v_0" initial_value="2"/>
<variable units="uM_per_min" name="v_1" cmeta:id="v_1" initial_value="1"/>
<variable units="dimensionless" public_interface="in" name="beta"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="V_in_maths">
<apply id="V_in"><eq/>
<ci>V_in</ci>
<apply><plus/>
<ci>v_0</ci>
<apply><times/>
<ci>v_1</ci>
<ci>beta</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_2" cmeta:id="V_2_component">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
<rdf:Description rdf:about="#V_2_component">Component for the calculation of V_2</rdf:Description>
<rdf:Description rdf:about="#V_2">Ca2+ pumping rate into the Ca2+ pool</rdf:Description>
<rdf:Description rdf:about="#V_M2">Maximum Ca2+ pumping rate into the Ca2+ pool</rdf:Description>
<rdf:Description rdf:about="#K_2">Threshold concentration for Ca2+ pumping into the Ca2+ pool</rdf:Description>
</rdf:RDF>
<variable units="uM" public_interface="in" name="Z"/>
<variable units="uM_per_min" public_interface="out" name="V_2"/>
<variable units="uM_per_min" name="V_M2" initial_value="6.5"/>
<variable units="uM" name="K_2" initial_value="0.1"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="V_2_maths">
<apply id="V_2"><eq/>
<ci>V_2</ci>
<apply><times/>
<ci>V_M2</ci>
<apply><divide/>
<apply><power/>
<ci>Z</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<apply><plus/>
<apply><power/>
<ci>K_2</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<apply><power/>
<ci>Z</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="V_3" cmeta:id="V_3_component">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
<rdf:Description rdf:about="#V_3_component">Component for the calculation of V_3</rdf:Description>
<rdf:Description rdf:about="#V_3">Ca2+ release rate from the Ca2+ pool</rdf:Description>
<rdf:Description rdf:about="#K_y">Threshold concentration for Ca2+ release</rdf:Description>
<rdf:Description rdf:about="#K_z">Threshold concentration for activation by Ca2+</rdf:Description>
<rdf:Description rdf:about="#K_a">Threshold concentration for activation by IP3</rdf:Description>
</rdf:RDF>
<variable units="min" public_interface="in" private_interface="out" name="time"/>
<variable units="uM" public_interface="in" private_interface="out" name="Z"/>
<variable units="uM" public_interface="in" name="Y"/>
<variable units="uM" private_interface="in" name="A"/>
<variable units="uM_per_min" public_interface="out" name="V_3" cmeta:id="V_3"/>
<variable units="uM" name="K_y" cmeta:id="K_y" initial_value="0.2"/>
<variable units="uM" name="K_z" cmeta:id="K_z" initial_value="0.3"/>
<variable units="uM" name="K_a" cmeta:id="K_a" initial_value="0.2"/>
<variable units="uM_per_min" name="V_M3" initial_value="19.5"/>
<variable units="dimensionless" public_interface="in" private_interface="out" name="beta"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="V_3_maths">
<apply id="V_3"><eq/>
<ci>V_3</ci>
<apply><times/>
<ci>V_M3</ci>
<apply><divide/>
<apply><power/>
<ci>A</ci>
<cn cellml:units="dimensionless">4</cn>
</apply>
<apply><plus/>
<apply><power/>
<ci>K_a</ci>
<cn cellml:units="dimensionless">4</cn>
</apply>
<apply><power/>
<ci>A</ci>
<cn cellml:units="dimensionless">4</cn>
</apply>
</apply>
</apply>
<apply><divide/>
<apply><power/>
<ci>Y</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<apply><plus/>
<apply><power/>
<ci>K_y</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<apply><power/>
<ci>Y</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
<apply><divide/>
<apply><power/>
<ci>Z</ci>
<cn cellml:units="dimensionless">4</cn>
</apply>
<apply><plus/>
<apply><power/>
<ci>K_z</ci>
<cn cellml:units="dimensionless">4</cn>
</apply>
<apply><power/>
<ci>Z</ci>
<cn cellml:units="dimensionless">4</cn>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="A" cmeta:id="A_component">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#">
<rdf:Description rdf:about="#A_component">Component for the calculation of A</rdf:Description>
<rdf:Description rdf:about="#A">IP3 concentration</rdf:Description>
<rdf:Description rdf:about="#upsilon_p">Maximum rate of agonist-stimulated production of IP3</rdf:Description>
<rdf:Description rdf:about="#upsilon_d">Maximum rate of IP3 degradation stimulated by cytosolic Ca2+</rdf:Description>
<rdf:Description rdf:about="#K_p">Threshold concentration for IP3 degradation</rdf:Description>
<rdf:Description rdf:about="#K_d">Threshold concentration for Ca2+ activation of IP3 degradation</rdf:Description>
<rdf:Description rdf:about="#epsilon">Ca2+-independent decay of IP3</rdf:Description>
</rdf:RDF>
<variable units="min" public_interface="in" name="time"/>
<variable units="uM" public_interface="in" name="Z"/>
<variable units="uM" public_interface="out" name="A" cmeta:id="A" initial_value="0.5"/>
<variable units="dimensionless" public_interface="in" name="beta"/>
<variable units="uM_per_min" name="upsilon_p" cmeta:id="upsilon_p" initial_value="2.5"/>
<variable units="uM_per_min" name="upsilon_d" cmeta:id="upsilon_d" initial_value="80"/>
<variable units="uM" name="K_p" cmeta:id="K_p" initial_value="1"/>
<variable units="uM" name="K_d" cmeta:id="K_d" initial_value="0.4"/>
<variable units="dimensionless" name="n" initial_value="4"/>
<variable units="per_min" name="epsilon" cmeta:id="epsilon" initial_value="0.1"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="A_maths">
<apply id="dA/dt"><eq/>
<apply><diff/>
<bvar><ci>time</ci></bvar>
<ci>A</ci>
</apply>
<apply><minus/>
<apply><minus/>
<apply><times/>
<ci>beta</ci>
<ci>upsilon_p</ci>
</apply>
<apply><times/>
<ci>upsilon_d</ci>
<apply><divide/>
<apply><power/>
<ci>A</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<apply><plus/>
<apply><power/>
<ci>K_p</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
<apply><power/>
<ci>A</ci>
<cn cellml:units="dimensionless">2</cn>
</apply>
</apply>
</apply>
<apply><divide/>
<apply><power/>
<ci>Z</ci>
<ci>n</ci>
</apply>
<apply><plus/>
<apply><power/>
<ci>K_d</ci>
<ci>n</ci>
</apply>
<apply><power/>
<ci>Z</ci>
<ci>n</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply><times/>
<ci>epsilon</ci>
<ci>A</ci>
</apply>
</apply>
</apply>
</math>
</component>
<!-- groups -->
<group>
<relationship_ref relationship="encapsulation"/>
<component_ref component="Ca">
<component_ref component="Ca_flux">
<component_ref component="V_in"/>
<component_ref component="V_2"/>
<component_ref component="V_3">
<component_ref component="A"/>
</component_ref>
</component_ref>
</component_ref>
</group>
<!-- connections -->
<connection>
<map_components component_1="environment" component_2="Ca"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Ca" component_2="Ca_flux"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="V_in" variable_2="V_in"/>
<map_variables variable_1="V_2" variable_2="V_2"/>
<map_variables variable_1="V_3" variable_2="V_3"/>
<map_variables variable_1="Z" variable_2="Z"/>
<map_variables variable_1="Y" variable_2="Y"/>
</connection>
<connection>
<map_components component_1="Ca_flux" component_2="V_in"/>
<map_variables variable_1="beta" variable_2="beta"/>
<map_variables variable_1="V_in" variable_2="V_in"/>
</connection>
<connection>
<map_components component_1="Ca_flux" component_2="V_2"/>
<map_variables variable_1="V_2" variable_2="V_2"/>
<map_variables variable_1="Z" variable_2="Z"/>
</connection>
<connection>
<map_components component_1="Ca_flux" component_2="V_3"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="beta" variable_2="beta"/>
<map_variables variable_1="V_3" variable_2="V_3"/>
<map_variables variable_1="Z" variable_2="Z"/>
<map_variables variable_1="Y" variable_2="Y"/>
</connection>
<connection>
<map_components component_1="V_3" component_2="A"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="Z" variable_2="Z"/>
<map_variables variable_1="A" variable_2="A"/>
<map_variables variable_1="beta" variable_2="beta"/>
</connection>
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">
<rdf:Description rdf:about="">
<dc:creator rdf:parseType="Resource">
<vCard:N rdf:parseType="Resource">
<vCard:Family>Hanna</vCard:Family>
<vCard:Given>Mark</vCard:Given>
<vCard:Other>James</vCard:Other>
</vCard:N>
<vCard:EMAIL rdf:parseType="Resource">
<rdf:value>mark@hanna.net.nz</rdf:value>
<rdf:type rdf:resource="http://imc.org/vCard/3.0#internet"/>
</vCard:EMAIL>
<vCard:ORG rdf:parseType="Resource">
<vCard:Orgname>The University of Auckland</vCard:Orgname>
<vCard:Orgunit>Auckland Bioengineering Institute</vCard:Orgunit>
</vCard:ORG>
</dc:creator>
<dcterms:created rdf:parseType="Resource">
<dcterms:W3CDTF>2009-11-30</dcterms:W3CDTF>
</dcterms:created>
</rdf:Description>
<rdf:Description rdf:about="borghans_model_1997a">
<dc:title>Complex intracellular calcium oscillations. A theoretical exploration of possible mechanisms</dc:title>
<bqs:reference rdf:parseType="Resource">
<dc:subject rdf:parseType="Resource">
<rdf:value>
<rdf:Bag>
<rdf:li>Calcium Signalling</rdf:li>
<rdf:li>Calcium Oscillations</rdf:li>
<rdf:li>Bursting</rdf:li>
<rdf:li>Chaos</rdf:li>
<rdf:li>Calcium Dynamics</rdf:li>
</rdf:Bag>
</rdf:value>
</dc:subject>
</bqs:reference>
<bqs:reference rdf:praseType="Resource">
<bqs:Pubmed_id>17029867</bqs:Pubmed_id>
<bqs:JournalArticle rdf:parseType="Resource">
<dc:creator>
<rdf:Seq>
<rdf:li rdf:parseType="Resource">
<bqs:Person rdf:parseType="Resource">
<vCard:N rdf:parseType="Resource">
<vCard:Family>Borghans</vCard:Family>
<vCard:Given>Jose</vCard:Given>
<vCard:Other>O.M.</vCard:Other>
</vCard:N>
</bqs:Person>
</rdf:li>
<rdf:li rdf:parseType="Resource">
<bqs:Person rdf:parseType="Resource">
<vCard:N rdf:parseType="Resource">
<vCard:Family>Dupont</vCard:Family>
<vCard:Given>Genevieve</vCard:Given>
</vCard:N>
</bqs:Person>
</rdf:li>
<rdf:li rdf:parseType="Resource">
<bqs:Person rdf:parseType="Resource">
<vCard:N rdf:parseType="Resource">
<vCard:Family>Goldbeter</vCard:Family>
<vCard:Given>Albert</vCard:Given>
</vCard:N>
</bqs:Person>
</rdf:li>
</rdf:Seq>
</dc:creator>
<dc:title>Complex intracellular calcium oscillations. A theoretical exploration of possible mechanisms</dc:title>
<dcterms:issued rdf:parseType="Resource">
<dcterms:W3CDTF>1997-01-16</dcterms:W3CDTF>
</dcterms:issued>
<bqs:Journal rdf:parseType="Resource">
<dc:title>Biophysical Chemistry</dc:title>
</bqs:Journal>
<bqs:volume>66</bqs:volume>
<bqs:first_page>25</bqs:first_page>
<bqs:last_page>41</bqs:last_page>
</bqs:JournalArticle>
</bqs:reference>
</rdf:Description>
</rdf:RDF>
</model>