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<articleinfo>
<title>A kinetic model of the thiazide-sensitive Na-Cl cotransporter</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Auckland Bioengineering Institute, The University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This CellML model runs in OpenCell and COR. The units have ben checked and they are consistent. We are unsure whether or not the model recreates the published results as there are no simple figures of changing concentration against time. Also sodium and chloride are set to constant values in this model - we suspect we need to derive an ODE equation based on the reaction figure (fig 1) in the paper.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
ABSTRACT: The aim of this study was to construct a numerical model of the thiazide-sensitive Na-Cl cotransporter (TSC) that can predict kinetics of thiazide binding and substrate transport of TSC. We hypothesized that the mechanisms underlying these kinetic properties can be approximated by a state diagram in which the transporter has two binding sites, one for sodium and another for chloride and thiazide. On the basis of the state diagram, a system of linear equations that should be satisfied in the steady state was postulated. Numerical solution of these equations yielded model prediction of kinetics of thiazide binding and substrate transport. Rate constants, which determine transitional rates between states, were systematically adjusted to minimize a penalty function that was devised to quantitatively estimate the difference between model predictions and experimental results. With the resultant rate constants, the model could simulate the following experimental results: 1) dissociation constant of thiazide in the absence of sodium and chloride; 2) inhibitory effect of chloride on thiazide binding; 3) stimulatory effect of sodium on thiazide binding; 4) combined effects of sodium and chloride on thiazide binding; 5) dependence of sodium influx on extracellular sodium and chloride; and 6) inhibition of sodium influx by extracellular thiazide. We conclude that known kinetic properties of TSC can be predicted by a model which is based on a state diagram.
</para>
<para>
The original paper reference is cited below:
</para>
<para>
A kinetic model of the thiazide-sensitive Na-Cl cotransporter, Hangil Chang and Toshiro Fujita, 1999,
<emphasis>American Journal of Physiology</emphasis>, 276, F952-F959. <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/10362783">PubMed ID: 10362783</ulink>
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>diagram of the model</title>
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<imagedata fileref="chang_1999.png"/>
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<caption>State diagram for the thiazide-sensitive Na-Cl cotransporter (TSC). Transporter (E) has binding sites for sodium (Na ) and chloride (Cl). Thiazide diuretics (D) compete with chloride for the same binding site. <emphasis>_i</emphasis> is used to indicate which symbols belong to the intracellular side.</caption>
</informalfigure>
</sect1>
</article>
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<dc:title>A kinetic model of the thiazide-sensitive Na-Cl cotransporter</dc:title>
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<variable units="millimolar" public_interface="in" name="ECl"/>
<variable units="millimolar" public_interface="in" name="ENaCl_"/>
<variable units="millimolar" public_interface="in" name="Na"/>
<variable units="millimolar" public_interface="in" name="Cl"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> ENaCl </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci> k5 </ci>
<ci> Cl </ci>
<ci> ENa </ci>
</apply>
<apply>
<times/>
<ci> k7 </ci>
<ci> Na </ci>
<ci> ECl </ci>
</apply>
<apply>
<times/>
<ci> k20 </ci>
<ci> ENaCl_ </ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> k6 </ci>
<ci> ENaCl </ci>
</apply>
<apply>
<times/>
<ci> k8 </ci>
<ci> ENaCl </ci>
</apply>
<apply>
<times/>
<ci> k19 </ci>
<ci> ENaCl </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="ENaCl_" cmeta:id="ENaCl_">
<variable units="millimolar" public_interface="out" initial_value="0.08333" name="ENaCl_"/>
<variable units="second_order_rate_constant" public_interface="in" name="k15"/>
<variable units="first_order_rate_constant" public_interface="in" name="k16"/>
<variable units="second_order_rate_constant" public_interface="in" name="k13"/>
<variable units="first_order_rate_constant" public_interface="in" name="k14"/>
<variable units="first_order_rate_constant" public_interface="in" name="k19"/>
<variable units="first_order_rate_constant" public_interface="in" name="k20"/>
<variable units="millimolar" public_interface="in" name="ENa_"/>
<variable units="millimolar" public_interface="in" name="ECl_"/>
<variable units="millimolar" public_interface="in" name="ENaCl"/>
<variable units="millimolar" public_interface="in" name="Na_"/>
<variable units="millimolar" public_interface="in" name="Cl_"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> ENaCl_ </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci> k13 </ci>
<ci> Cl_ </ci>
<ci> ENa_ </ci>
</apply>
<apply>
<times/>
<ci> k15 </ci>
<ci> Na_ </ci>
<ci> ECl_ </ci>
</apply>
<apply>
<times/>
<ci> k19 </ci>
<ci> ENaCl </ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> k14 </ci>
<ci> ENaCl_ </ci>
</apply>
<apply>
<times/>
<ci> k16 </ci>
<ci> ENaCl_ </ci>
</apply>
<apply>
<times/>
<ci> k20 </ci>
<ci> ENaCl_ </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="reaction_constants">
<variable units="second_order_rate_constant" public_interface="out" name="k1" initial_value="1.0E5"/>
<variable units="first_order_rate_constant" public_interface="out" name="k2" initial_value="4.183E5"/>
<variable units="second_order_rate_constant" public_interface="out" name="k3" initial_value="1.0E5"/>
<variable units="first_order_rate_constant" public_interface="out" name="k4" initial_value="4.928E6"/>
<variable units="second_order_rate_constant" public_interface="out" name="k5" initial_value="1.0E5"/>
<variable units="first_order_rate_constant" public_interface="out" name="k6" initial_value="1.065E6"/>
<variable units="second_order_rate_constant" public_interface="out" name="k7" initial_value="1.0E5"/>
<variable units="first_order_rate_constant" public_interface="out" name="k8" initial_value="8.940E4"/>
<variable units="second_order_rate_constant" public_interface="out" name="k9" initial_value="1.0E5"/>
<variable units="first_order_rate_constant" public_interface="out" name="k10" initial_value="4.183E5"/>
<variable units="second_order_rate_constant" public_interface="out" name="k11" initial_value="1.0E5"/>
<variable units="first_order_rate_constant" public_interface="out" name="k12" initial_value="4.982E6"/>
<variable units="second_order_rate_constant" public_interface="out" name="k13" initial_value="1.0E5"/>
<variable units="first_order_rate_constant" public_interface="out" name="k14" initial_value="1.065E6"/>
<variable units="second_order_rate_constant" public_interface="out" name="k15" initial_value="1.0E5"/>
<variable units="first_order_rate_constant" public_interface="out" name="k16" initial_value="8.940E4"/>
<variable units="first_order_rate_constant" public_interface="out" name="k17" initial_value="4.587E5"/>
<variable units="first_order_rate_constant" public_interface="out" name="k18" initial_value="1.0E5"/>
<variable units="first_order_rate_constant" public_interface="out" name="k19" initial_value="1.0E3"/>
<variable units="first_order_rate_constant" public_interface="out" name="k20" initial_value="2.180E2"/>
<variable units="second_order_rate_constant" public_interface="out" name="k21" initial_value="1.0E5"/>
<variable units="first_order_rate_constant" public_interface="out" name="k22" initial_value="4.183E5"/>
<variable units="second_order_rate_constant" public_interface="out" name="k23" initial_value="1.0E5"/>
<variable units="first_order_rate_constant" public_interface="out" name="k24" initial_value="3.192E1"/>
<variable units="second_order_rate_constant" public_interface="out" name="k25" initial_value="1.0E5"/>
<variable units="first_order_rate_constant" public_interface="out" name="k26" initial_value="3.192E1"/>
<variable units="second_order_rate_constant" public_interface="out" name="k27" initial_value="1.0E5"/>
<variable units="first_order_rate_constant" public_interface="out" name="k28" initial_value="1.389E5"/>
<variable units="second_order_rate_constant" public_interface="out" name="k29" initial_value="1.0E5"/>
<variable units="first_order_rate_constant" public_interface="out" name="k30" initial_value="3.514E-1"/>
<variable units="second_order_rate_constant" public_interface="out" name="k31" initial_value="1.0E5"/>
<variable units="first_order_rate_constant" public_interface="out" name="k32" initial_value="1.166E-1"/>
<variable units="millimolar" public_interface="out" name="Na" initial_value="50.0"/>
<variable units="millimolar" public_interface="out" name="Cl" initial_value="96.0"/>
<variable units="millimolar" public_interface="out" name="D" initial_value="1.0E-6"/>
<variable units="millimolar" public_interface="out" name="Cl_" initial_value="40.0"/>
<variable units="millimolar" public_interface="out" name="Na_" initial_value="10.0"/>
<variable units="millimolar" public_interface="out" name="D_" initial_value="1.0E-6"/>
</component>
<connection>
<map_components component_2="environment" component_1="E"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="E_"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="ENa"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="ENa_"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="ED"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="ED_"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="ECl"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="ECl_"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="ENaD"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="ENaD_"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="ENaCl"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="ENaCl_"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="ED" component_1="E"/>
<map_variables variable_2="E" variable_1="E"/>
<map_variables variable_2="ED" variable_1="ED"/>
</connection>
<connection>
<map_components component_2="ED_" component_1="E_"/>
<map_variables variable_2="E_" variable_1="E_"/>
<map_variables variable_2="ED_" variable_1="ED_"/>
</connection>
<connection>
<map_components component_2="ENa" component_1="E"/>
<map_variables variable_2="E" variable_1="E"/>
<map_variables variable_2="ENa" variable_1="ENa"/>
</connection>
<connection>
<map_components component_2="ENa_" component_1="E_"/>
<map_variables variable_2="E_" variable_1="E_"/>
<map_variables variable_2="ENa_" variable_1="ENa_"/>
</connection>
<connection>
<map_components component_2="ECl" component_1="E"/>
<map_variables variable_2="E" variable_1="E"/>
<map_variables variable_2="ECl" variable_1="ECl"/>
</connection>
<connection>
<map_components component_2="ECl_" component_1="E_"/>
<map_variables variable_2="E_" variable_1="E_"/>
<map_variables variable_2="ECl_" variable_1="ECl_"/>
</connection>
<connection>
<map_components component_2="E_" component_1="E"/>
<map_variables variable_2="E" variable_1="E"/>
<map_variables variable_2="E_" variable_1="E_"/>
</connection>
<connection>
<map_components component_2="ED" component_1="ENaD"/>
<map_variables variable_2="ENaD" variable_1="ENaD"/>
<map_variables variable_2="ED" variable_1="ED"/>
</connection>
<connection>
<map_components component_2="ED_" component_1="ENaD_"/>
<map_variables variable_2="ENaD_" variable_1="ENaD_"/>
<map_variables variable_2="ED_" variable_1="ED_"/>
</connection>
<connection>
<map_components component_2="ENa" component_1="ENaD"/>
<map_variables variable_2="ENaD" variable_1="ENaD"/>
<map_variables variable_2="ENa" variable_1="ENa"/>
</connection>
<connection>
<map_components component_2="ENa_" component_1="ENaD_"/>
<map_variables variable_2="ENaD_" variable_1="ENaD_"/>
<map_variables variable_2="ENa_" variable_1="ENa_"/>
</connection>
<connection>
<map_components component_2="ENa" component_1="ENaCl"/>
<map_variables variable_2="ENaCl" variable_1="ENaCl"/>
<map_variables variable_2="ENa" variable_1="ENa"/>
</connection>
<connection>
<map_components component_2="ENa_" component_1="ENaCl_"/>
<map_variables variable_2="ENaCl_" variable_1="ENaCl_"/>
<map_variables variable_2="ENa_" variable_1="ENa_"/>
</connection>
<connection>
<map_components component_2="ECl" component_1="ENaCl"/>
<map_variables variable_2="ENaCl" variable_1="ENaCl"/>
<map_variables variable_2="ECl" variable_1="ECl"/>
</connection>
<connection>
<map_components component_2="ECl_" component_1="ENaCl_"/>
<map_variables variable_2="ENaCl_" variable_1="ENaCl_"/>
<map_variables variable_2="ECl_" variable_1="ECl_"/>
</connection>
<connection>
<map_components component_2="ENaCl" component_1="ENaCl_"/>
<map_variables variable_2="ENaCl_" variable_1="ENaCl_"/>
<map_variables variable_2="ENaCl" variable_1="ENaCl"/>
</connection>
<connection>
<map_components component_2="reaction_constants" component_1="E"/>
<map_variables variable_2="k23" variable_1="k23"/>
<map_variables variable_2="k24" variable_1="k24"/>
<map_variables variable_2="k1" variable_1="k1"/>
<map_variables variable_2="k2" variable_1="k2"/>
<map_variables variable_2="k3" variable_1="k3"/>
<map_variables variable_2="k4" variable_1="k4"/>
<map_variables variable_2="k17" variable_1="k17"/>
<map_variables variable_2="k18" variable_1="k18"/>
<map_variables variable_2="Cl" variable_1="Cl"/>
<map_variables variable_2="Na" variable_1="Na"/>
<map_variables variable_2="D" variable_1="D"/>
</connection>
<connection>
<map_components component_2="reaction_constants" component_1="ED"/>
<map_variables variable_2="k23" variable_1="k23"/>
<map_variables variable_2="k24" variable_1="k24"/>
<map_variables variable_2="k21" variable_1="k21"/>
<map_variables variable_2="k22" variable_1="k22"/>
<map_variables variable_2="D" variable_1="D"/>
<map_variables variable_2="Na" variable_1="Na"/>
</connection>
<connection>
<map_components component_2="reaction_constants" component_1="ENaD"/>
<map_variables variable_2="k21" variable_1="k21"/>
<map_variables variable_2="k22" variable_1="k22"/>
<map_variables variable_2="k25" variable_1="k25"/>
<map_variables variable_2="k26" variable_1="k26"/>
<map_variables variable_2="Na" variable_1="Na"/>
<map_variables variable_2="D" variable_1="D"/>
</connection>
<connection>
<map_components component_2="reaction_constants" component_1="ENa"/>
<map_variables variable_2="k25" variable_1="k25"/>
<map_variables variable_2="k26" variable_1="k26"/>
<map_variables variable_2="k1" variable_1="k1"/>
<map_variables variable_2="k2" variable_1="k2"/>
<map_variables variable_2="k5" variable_1="k5"/>
<map_variables variable_2="k6" variable_1="k6"/>
<map_variables variable_2="Cl" variable_1="Cl"/>
<map_variables variable_2="Na" variable_1="Na"/>
<map_variables variable_2="D" variable_1="D"/>
</connection>
<connection>
<map_components component_2="reaction_constants" component_1="ECl"/>
<map_variables variable_2="k7" variable_1="k7"/>
<map_variables variable_2="k8" variable_1="k8"/>
<map_variables variable_2="k3" variable_1="k3"/>
<map_variables variable_2="k4" variable_1="k4"/>
<map_variables variable_2="Cl" variable_1="Cl"/>
<map_variables variable_2="Na" variable_1="Na"/>
</connection>
<connection>
<map_components component_2="reaction_constants" component_1="ENaCl"/>
<map_variables variable_2="k7" variable_1="k7"/>
<map_variables variable_2="k8" variable_1="k8"/>
<map_variables variable_2="k5" variable_1="k5"/>
<map_variables variable_2="k6" variable_1="k6"/>
<map_variables variable_2="k19" variable_1="k19"/>
<map_variables variable_2="k20" variable_1="k20"/>
<map_variables variable_2="Cl" variable_1="Cl"/>
<map_variables variable_2="Na" variable_1="Na"/>
</connection>
<connection>
<map_components component_2="reaction_constants" component_1="E_"/>
<map_variables variable_2="k29" variable_1="k29"/>
<map_variables variable_2="k30" variable_1="k30"/>
<map_variables variable_2="k11" variable_1="k11"/>
<map_variables variable_2="k12" variable_1="k12"/>
<map_variables variable_2="k9" variable_1="k9"/>
<map_variables variable_2="k10" variable_1="k10"/>
<map_variables variable_2="k17" variable_1="k17"/>
<map_variables variable_2="k18" variable_1="k18"/>
<map_variables variable_2="Cl_" variable_1="Cl_"/>
<map_variables variable_2="Na_" variable_1="Na_"/>
<map_variables variable_2="D_" variable_1="D_"/>
</connection>
<connection>
<map_components component_2="reaction_constants" component_1="ED_"/>
<map_variables variable_2="k29" variable_1="k29"/>
<map_variables variable_2="k30" variable_1="k30"/>
<map_variables variable_2="k27" variable_1="k27"/>
<map_variables variable_2="k28" variable_1="k28"/>
<map_variables variable_2="D_" variable_1="D_"/>
<map_variables variable_2="Na_" variable_1="Na_"/>
</connection>
<connection>
<map_components component_2="reaction_constants" component_1="ENaD_"/>
<map_variables variable_2="k27" variable_1="k27"/>
<map_variables variable_2="k28" variable_1="k28"/>
<map_variables variable_2="k31" variable_1="k31"/>
<map_variables variable_2="k32" variable_1="k32"/>
<map_variables variable_2="Na_" variable_1="Na_"/>
<map_variables variable_2="D_" variable_1="D_"/>
</connection>
<connection>
<map_components component_2="reaction_constants" component_1="ENa_"/>
<map_variables variable_2="k31" variable_1="k31"/>
<map_variables variable_2="k32" variable_1="k32"/>
<map_variables variable_2="k9" variable_1="k9"/>
<map_variables variable_2="k10" variable_1="k10"/>
<map_variables variable_2="k13" variable_1="k13"/>
<map_variables variable_2="k14" variable_1="k14"/>
<map_variables variable_2="Cl_" variable_1="Cl_"/>
<map_variables variable_2="Na_" variable_1="Na_"/>
<map_variables variable_2="D_" variable_1="D_"/>
</connection>
<connection>
<map_components component_2="reaction_constants" component_1="ECl_"/>
<map_variables variable_2="k11" variable_1="k11"/>
<map_variables variable_2="k12" variable_1="k12"/>
<map_variables variable_2="k15" variable_1="k15"/>
<map_variables variable_2="k16" variable_1="k16"/>
<map_variables variable_2="Cl_" variable_1="Cl_"/>
<map_variables variable_2="Na_" variable_1="Na_"/>
</connection>
<connection>
<map_components component_2="reaction_constants" component_1="ENaCl_"/>
<map_variables variable_2="k15" variable_1="k15"/>
<map_variables variable_2="k16" variable_1="k16"/>
<map_variables variable_2="k13" variable_1="k13"/>
<map_variables variable_2="k14" variable_1="k14"/>
<map_variables variable_2="k19" variable_1="k19"/>
<map_variables variable_2="k20" variable_1="k20"/>
<map_variables variable_2="Cl_" variable_1="Cl_"/>
<map_variables variable_2="Na_" variable_1="Na_"/>
</connection>
<rdf:RDF>
<rdf:Bag rdf:about="rdf:#0bb854d1-3425-4cba-92ed-6908aff6b72f">
<rdf:li>kidney</rdf:li>
<rdf:li>electrophysiology</rdf:li>
</rdf:Bag>
<rdf:Seq rdf:about="rdf:#327461b8-2a5f-48fd-baa2-a1b0bfa03aa1">
<rdf:li rdf:resource="rdf:#3c05e2a2-0758-4b6a-ba9e-e7b56daf1cfc"/>
<rdf:li rdf:resource="rdf:#91d96927-3af0-44cd-b73c-5a2f39ac25f8"/>
</rdf:Seq>
<rdf:Description rdf:about="#ENaCl_i">
<dcterms:alternative>
Intracellular Transporter-Sodium-Chloride Complex
</dcterms:alternative>
<dc:title>ENaCl_i</dc:title>
</rdf:Description>
<rdf:Description rdf:about="">
<dc:publisher>The University of Auckland, Auckland Bioengineering Institute</dc:publisher>
<cmeta:comment rdf:resource="rdf:#c757deb0-f55b-4c45-b2b0-83e8cbb36b30"/>
<dcterms:created rdf:resource="rdf:#7d344280-89c4-476a-9759-2defb83ca1cb"/>
<dc:creator rdf:resource="rdf:#55f6976c-a732-491e-a33b-43921256764c"/>
<cmeta:modification rdf:resource="rdf:#329489e5-895a-48e5-a456-f3f145d82e2c"/>
<cmeta:modification rdf:resource="rdf:#a15ed80f-b207-4f3f-8f94-d07bfc23f973"/>
</rdf:Description>
<rdf:Description rdf:about="#E">
<dcterms:alternative>Extracellular Transporter</dcterms:alternative>
<dc:title>E</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#297d5548-8c46-4515-b053-80d681025204">
<vCard:Given/>
<vCard:Family/>
<vCard:Other/>
</rdf:Description>
<rdf:Description rdf:about="#E_">
<dcterms:alternative>Intracellular Transporter</dcterms:alternative>
<dc:title>E_</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#29c527b6-239c-48ff-85da-34ac26662c99">
<dc:subject rdf:resource="rdf:#f286d41d-023a-4f08-8694-c266c039eee4"/>
</rdf:Description>
<rdf:Description rdf:about="#ED">
<dcterms:alternative>
Extracellular Transporter-Thiazide Diuretics Complex
</dcterms:alternative>
<dc:title>ED</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#37ac1892-aab1-45e8-9c2a-0b3560d86e09">
<vCard:Given>Hangil</vCard:Given>
<vCard:Family>Chang</vCard:Family>
</rdf:Description>
<rdf:Description rdf:about="#ENa_">
<dcterms:alternative>
Intracellular Transporter-Sodium Complex
</dcterms:alternative>
<dc:title>ENa_</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#ENaCl">
<dcterms:alternative>
Extracellular Transporter-Sodium-Chloride Complex
</dcterms:alternative>
<dc:title>ENaCl</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#0fbb439a-0944-4bbc-acc2-c4cab1412a18">
<dcterms:W3CDTF>2007-06-05T09:16:58+12:00</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#f54c91a1-3fef-4213-970d-f7711d4f515c">
<dcterms:W3CDTF>2007-06-25T13:20:00+12:00</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#fa457412-afdd-4f70-bd1d-e4789f0a5185">
<vCard:N rdf:resource="rdf:#5a803520-6fbb-4ff5-a2ec-cab9c84b6c18"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#5a803520-6fbb-4ff5-a2ec-cab9c84b6c18">
<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#f286d41d-023a-4f08-8694-c266c039eee4">
<bqs:subject_type>keyword</bqs:subject_type>
<rdf:value rdf:resource="rdf:#0bb854d1-3425-4cba-92ed-6908aff6b72f"/>
</rdf:Description>
<rdf:Description rdf:about="#ECl">
<dcterms:alternative>
Extracellular Transporter-Chloride Complex
</dcterms:alternative>
<dc:title>ECl</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#901cb097-744d-451c-822f-1943ed49c4f2">
<dc:creator rdf:resource="rdf:#8c884d73-01b7-4eeb-9206-ac93b3d6c7e6"/>
<rdf:value>This is the CellML description of Chang and Fujita's 1999 kinetic model of the thiazide-sensitive Na-Cl cotransporter of the renal distal tubule. This model can be run in PCEnv but it gives a flat output. I suspect it needs to be embedded within a whole cell model in order to give a reasonable output.</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#0a54e363-d4b6-4e5b-aee7-62938ac143b4">
<vCard:Orgname>The University of Auckland</vCard:Orgname>
<vCard:Orgunit>Auckland Bioengineering Institute</vCard:Orgunit>
</rdf:Description>
<rdf:Description rdf:about="#chang_1999">
<dc:title>
Chang and Fujita's 1999 kinetic model of the thiazide-sensitive Na-Cl cotransporter of the renal distal tubule.
</dc:title>
<cmeta:bio_entity>Renal Distal Tubule</cmeta:bio_entity>
<cmeta:comment rdf:resource="rdf:#901cb097-744d-451c-822f-1943ed49c4f2"/>
<bqs:reference rdf:resource="rdf:#29c527b6-239c-48ff-85da-34ac26662c99"/>
<bqs:reference rdf:resource="rdf:#8a9e357a-bc78-490c-a99e-cf397fba4240"/>
</rdf:Description>
<rdf:Description rdf:about="#ECl_i">
<dcterms:alternative>
Intracellular Transporter-Chloride Complex
</dcterms:alternative>
<dc:title>ECl_</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#cd2c94aa-dae0-4b2c-be83-be425f1ac5cc">
<vCard:FN>Catherine Lloyd</vCard:FN>
</rdf:Description>
<rdf:Description rdf:about="rdf:#55f6976c-a732-491e-a33b-43921256764c">
<vCard:ORG rdf:resource="rdf:#0a54e363-d4b6-4e5b-aee7-62938ac143b4"/>
<vCard:EMAIL rdf:resource="rdf:#77c698bc-03ae-4953-a23b-aeba899ad4d2"/>
<vCard:N rdf:resource="rdf:#e83ba270-d118-43c5-8877-bf5fed03f2dd"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#9e0eecbc-2c2a-4d42-8b75-6ba6c1bc718a">
<dc:title>American Journal of Physiology</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#ENa">
<dcterms:alternative>
Extracellular Transporter-Sodium Complex
</dcterms:alternative>
<dc:title>ENa</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#91d96927-3af0-44cd-b73c-5a2f39ac25f8">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
<vCard:N rdf:resource="rdf:#ad2242ed-8d2c-49f2-9e7c-57487a1527ab"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#e83ba270-d118-43c5-8877-bf5fed03f2dd">
<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#a15ed80f-b207-4f3f-8f94-d07bfc23f973">
<dcterms:modified rdf:resource="rdf:#0fbb439a-0944-4bbc-acc2-c4cab1412a18"/>
<rdf:value>The new version of this model has been re-coded to remove the reaction element and replace it with a simple MathML description of the model reaction kinetics. This is thought to be truer to the original publication, and information regarding the enzyme kinetics etc will later be added to the metadata through use of an ontology.
The model runs in the PCEnv simulator but gives a flat output.</rdf:value>
<cmeta:modifier rdf:resource="rdf:#fa457412-afdd-4f70-bd1d-e4789f0a5185"/>
</rdf:Description>
<rdf:Description rdf:about="#ED_">
<dcterms:alternative>
Intracellular Transporter-Thiazide Diuretics Complex
</dcterms:alternative>
<dc:title>ED_</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#ENaD">
<dcterms:alternative>
Extracellular Transporter-Thiazide Diuretics-Sodium Complex
</dcterms:alternative>
<dc:title>ENaD</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#c757deb0-f55b-4c45-b2b0-83e8cbb36b30">
<dc:creator rdf:resource="rdf:#cd2c94aa-dae0-4b2c-be83-be425f1ac5cc"/>
<rdf:value>The new version of this model has been re-coded to remove the reaction element and replace it with a simple MathML description of the model reaction kinetics. This is thought to be truer to the original publication, and information regarding the enzyme kinetics etc will later be added to the metadata through use of an ontology.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#77c698bc-03ae-4953-a23b-aeba899ad4d2">
<rdf:type rdf:resource="http://imc.org/vCard/3.0#internet"/>
<rdf:value>c.lloyd@auckland.ac.nz</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#8a9e357a-bc78-490c-a99e-cf397fba4240">
<bqs:Pubmed_id>10362783</bqs:Pubmed_id>
<bqs:JournalArticle rdf:resource="rdf:#077e8ed7-4af5-45d7-a2c9-2ce274da2919"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#ad2242ed-8d2c-49f2-9e7c-57487a1527ab">
<vCard:Given>Toshiro</vCard:Given>
<vCard:Family>Fujita</vCard:Family>
</rdf:Description>
<rdf:Description rdf:about="rdf:#008af2c6-84a7-4662-b52d-b551408bc782">
<vCard:N rdf:resource="rdf:#297d5548-8c46-4515-b053-80d681025204"/>
</rdf:Description>
<rdf:Description rdf:about="#ENaD_">
<dcterms:alternative>
Intracellular Transporter-Thiazide Diuretics-Sodium Complex
</dcterms:alternative>
<dc:title>ENaD_</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#3c05e2a2-0758-4b6a-ba9e-e7b56daf1cfc">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
<vCard:N rdf:resource="rdf:#37ac1892-aab1-45e8-9c2a-0b3560d86e09"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#329489e5-895a-48e5-a456-f3f145d82e2c">
<dcterms:modified rdf:resource="rdf:#f54c91a1-3fef-4213-970d-f7711d4f515c"/>
<rdf:value>Removed reaction element and replaced with simple MathML</rdf:value>
<cmeta:modifier rdf:resource="rdf:#008af2c6-84a7-4662-b52d-b551408bc782"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#fa01433e-03c9-4f31-b53f-873f04246cd0">
<dcterms:W3CDTF>1999-06</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#7d344280-89c4-476a-9759-2defb83ca1cb">
<dcterms:W3CDTF>2007-05-28T00:00:00+00:00</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#077e8ed7-4af5-45d7-a2c9-2ce274da2919">
<dc:creator rdf:resource="rdf:#327461b8-2a5f-48fd-baa2-a1b0bfa03aa1"/>
<dc:title>A kinetic model of the thiazide-sensitive Na-Cl cotransporter</dc:title>
<bqs:volume>276</bqs:volume>
<bqs:first_page>F952</bqs:first_page>
<bqs:Journal rdf:resource="rdf:#9e0eecbc-2c2a-4d42-8b75-6ba6c1bc718a"/>
<dcterms:issued rdf:resource="rdf:#fa01433e-03c9-4f31-b53f-873f04246cd0"/>
<bqs:last_page>F959</bqs:last_page>
</rdf:Description>
<rdf:Description rdf:about="rdf:#8c884d73-01b7-4eeb-9206-ac93b3d6c7e6">
<vCard:FN>Catherine Lloyd</vCard:FN>
</rdf:Description>
</rdf:RDF>
</model>
