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Copy pathRxn_IP3R_DYK.xml
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Rxn_IP3R_DYK.xml
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<ReactionScheme>
<!-- Model based on: De Young GW, Keizer J. A single-pool inositol 1,4,5-trisphosphate-receptor-based model for agonist-stimulated oscillations in Ca2+ concentration. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9895-9. doi: 10.1073/pnas.89.20.9895. PMID: 1329108; PMCID: PMC50240. -->
<!-- Diffusion constant sources:-->
<!-- Concentrations are in nanomoles per liter Diffusion constants are in mu2/s -->
<Specie name="Ca" id="Ca" kdiff="175" kdiffunit="mu2/s"/>
<Specie name="CaOut" id="CaOut" kdiff="2." kdiffunit="mu2/s"/>
<!--Added from Andy's model-->
<Specie name="CaOutLeak" id="CaOutLeak" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Leak" id="Leak" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="InfluxER" id="InfluxER" kdiff="0"
kdiffunit="mu2/s"/>
<Specie name="CaOutInfluxER" id="CaOutInfluxER" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Calbin" id="Calbin" kdiff="9.25" kdiffunit="mu2/s"/>
<Specie name="CalbinC" id="CalbinC" kdiff="9.25" kdiffunit="mu2/s"/>
<Specie name="CaBCa" id="CaBCa" kdiff="10" kdiffunit="mu2/s"/>
<Specie name="CaB" id="CaB" kdiff="10" kdiffunit="mu2/s"/>
<!--Added from Andy's model-->
<Specie name="pmca" id="pmca" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="ncx" id="ncx" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pmcaCa" id="pmcaCa" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="ncxCa" id="ncxCa" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AC8" id="AC8" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AC8CaMCa4" id="AC8CaMCa4" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AC8CaMCa4ATP" id="AC8CaMCa4ATP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CaM" id="CaM" kdiff="11" kdiffunit="mu2/s"/>
<Specie name="CaMCa2" id="CaMCa2" kdiff="11" kdiffunit="mu2/s"/>
<Specie name="CaMCa4" id="CaMCa4" kdiff="11" kdiffunit="mu2/s"/>
<Specie name="Ng" id="Ng" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="NgCaM" id="NgCaM" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PP2B" id="PP2B" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PP2BCaM" id="PP2BCaM" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PP2BCaMCa2" id="PP2BCaMCa2" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PP2BCaMCa4" id="PP2BCaMCa4" kdiff="0"
kdiffunit="mu2/s"/>
<Specie name="CK" id="CK" kdiff="0.1" kdiffunit="mu2/s"/>
<Specie name="CKCaMCa4" id="CKCaMCa4" kdiff="0.1" kdiffunit="mu2/s"/>
<Specie name="CKpCaMCa4" id="CKpCaMCa4" kdiff="3.6" kdiffunit="mu2/s"/>
<Specie name="CKp" id="CKp" kdiff="3.6" kdiffunit="mu2/s"/>
<Specie name="CKpPP1" id="CKpPP1" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CKpCaMCa4PP1" id="CKpCaMCa4PP1" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PKA" id="PKA" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PKAcAMP2" id="PKAcAMP2" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PKAcAMP4" id="PKAcAMP4" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PKAr" id="PKAr" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PKAc" id="PKAc" kdiff="0.836" kdiffunit="mu2/s"/>
<Specie name="I1" id="I1" kdiff="9.49" kdiffunit="mu2/s"/>
<Specie name="I1PKAc" id="I1PKAc" kdiff="10.6" kdiffunit="mu2/s"/>
<Specie name="Ip35" id="Ip35" kdiff="7.02" kdiffunit="mu2/s"/>
<Specie name="Ip35PP1" id="Ip35PP1" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Ip35PP2BCaMCa4" id="Ip35PP2BCaMCa4" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Ip35PP1PP2BCaMCa4" id="Ip35PP1PP2BCaMCa4" kdiff="0" kdiffunit="mu2/s"/>
<!-- inactive CaMKII is immobile (at least the heteromeric fraction),-->
<Specie name="PP1" id="PP1" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Epac1" id="Epac1" kdiff="5.62" kdiffunit="mu2/s"/>
<Specie name="Epac1cAMP" id="Epac1cAMP" kdiff="5.61" kdiffunit="mu2/s"/>
<Specie name="cAMP" id="cAMP" kdiff="86.4" kdiffunit="mu2/s"/>
<Specie name="IP3R" id="IP3R" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="S100" id="S100" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="S110" id="S110" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="S101" id="S101" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="S011" id="S011" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="S010" id="S010" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="S001" id="S001" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="S111" id="S111" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CaER" id="CaER" kdiff="0." kdiffunit="mu2/s"/>
<Specie name="CaERLeak" id="CaERLeak" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="LeakER" id="LeakER" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="SERCA" id="SERCA" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="SERCACa2" id="SERCACa2" kdiff="0" kdiffunit="mu2/s"/>
<!--calreticulin-->
<Specie name="CRT" id="CRT" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="CRTP" id="CRTP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="ACh" id="ACh" kdiff="10" kdiffunit = "mu2/s"/>
<Specie name="m1R" id="m1R" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AChm1R" id="AChm1R" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="m1RGq" id="m1RGq" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="AChm1RGq" id="AChm1RGq" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Gqabg" id="Gqabg" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="GqaGTP" id="GqaGTP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="GqaGDP" id="GqaGDP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Gbg" id="Gbg" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Plc" id="Plc" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PlcCa" id="PlcCa" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PlcCaGqa" id="PlcCaGqa" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PlcGqa" id="PlcGqa" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PlcCaPip2" id="PlcCaPip2" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PlcCaGqaPip2" id="PlcCaGqaPip2" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="Dag" id="Dag" kdiff="0"
kdiffunit="mu2/s"/>
<Specie name="IP3" id="IP3" kdiff="10."
kdiffunit="mu2/s"/> <!--Hindered cytoplasmic diffusion of
inositol trisphosphate restricts its cellular range of
action George D. Dickinson1,*, Kyle L. Ellefsen1,
Silvina Ponce Dawson2, John E. Pearson3, and Ian Parker1,4
Sci signalling -->
<Specie name="Pip2" id="Pip2" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="IP3degrad" id="IP3degrad" kdiff="79.6" kdiffunit="mu2/s"/>
<Specie name="PIkinase" id="PIkinase" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="IP3degPIk" id="IP3degPIk" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PDE4" id="PDE4" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PDE4cAMP" id="PDE4cAMP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PKAcPDE4" id="PKAcPDE4" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pPDE4" id="pPDE4" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="pPDE4cAMP" id="pPDE4cAMP" kdiff="0" kdiffunit="mu2/s"/>
<Specie name="PKAc_PDE4_cAMP" id="PKAc_PDE4_cAMP" kdiff="0" kdiffunit="mu2/s"/>
<!--*************************************************************************
Now, the reactions themselves
**************************************************************************-->
<!--X. ***************************************************************************-->
<!-- -->
<!-- Ca pump high affinity - Ca + pmca <-> pmcaCa -->
<Reaction name = "Ca_pump1a" id="Ca_pump1a">
<Reactant specieID="Ca"/>
<Reactant specieID="pmca"/>
<Product specieID="pmcaCa"/>
<forwardRate>0.5e-4</forwardRate>
<reverseRate>0.007</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- Ca pump high affinity - pmcaCa <-> pmca + CaOut -->
<Reaction name = "Ca_pump1b" id="Ca_pump1b">
<Reactant specieID="pmcaCa"/>
<Product specieID="pmca"/>
<Product specieID="CaOut"/>
<forwardRate>0.0035</forwardRate>
<reverseRate>0</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- Ca leak - CaOut + Leak <-> CaOutLeak -->
<Reaction name = "Ca_leak" id="Ca_leaka">
<Reactant specieID="CaOut"/>
<Reactant specieID="Leak"/>
<Product specieID="CaOutLeak"/>
<forwardRate>1.5e-6</forwardRate>
<reverseRate>1.1e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- Ca leak - CaOutLeak <-> Ca + Leak -->
<Reaction name = "Ca_leak" id="Ca_leakb">
<Reactant specieID="CaOutLeak"/>
<Product specieID="Ca"/>
<Product specieID="Leak"/>
<forwardRate>1.1e-3</forwardRate>
<reverseRate>0</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- Ca leak - CaOut + Leak <-> CaOutLeak -->
<Reaction name = "Ca_influxER" id="Ca_cainfluxa">
<Reactant specieID="CaOut"/>
<Reactant specieID="InfluxER"/>
<Product specieID="CaOutInfluxER"/>
<forwardRate>1.5e-7</forwardRate>
<reverseRate>1.1e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- Ca leak - CaOutLeak <-> Ca + Leak -->
<Reaction name = "Ca_influxER" id="Ca_influxb">
<Reactant specieID="CaOutInfluxER"/>
<Product specieID="CaER"/>
<Product specieID="InfluxER"/>
<forwardRate>1.1e-4</forwardRate>
<reverseRate>0</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- Serca -->
<Reaction name = "SERCA_1a" id="SERCA_1a">
<Reactant specieID="Ca" n="2"/>
<Reactant specieID="SERCA"/>
<Product specieID="SERCACa2"/>
<forwardRate>0.0001</forwardRate>
<reverseRate>0.001</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- Ca pump high affinity - pmcaCa <-> pmca + CaOut -->
<Reaction name = "SERCA_1b" id="SERCA_1b">
<Reactant specieID="SERCACa2"/>
<Product specieID="SERCA"/>
<Product specieID="CaER" n="2"/>
<forwardRate>0.01</forwardRate>
<reverseRate>0</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- ER Ca leak - CaER+ LeakER <-> CaERLeak-->
<Reaction name = "Ca_leakER" id="Ca_leakaER">
<Reactant specieID="CaER"/>
<Reactant specieID="LeakER"/>
<Product specieID="CaERLeak"/>
<forwardRate>7.e-7</forwardRate>
<reverseRate>1.1e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- ER Ca leak - CaERLeak <-> Ca + LeakER-->
<Reaction name = "Ca_leakER" id="Ca_leakbER">
<Reactant specieID="CaERLeak"/>
<Product specieID="Ca"/>
<Product specieID="LeakER"/>
<forwardRate>2.5e-3</forwardRate>
<reverseRate>0</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- Ca Buffer Ca + Calbindin <-> calbinCa -->
<Reaction name = "Ca_buffer" id="Ca_Buffer">
<Reactant specieID="Ca"/>
<Reactant specieID="Calbin"/>
<Product specieID="CalbinC"/>
<forwardRate>2.8e-5</forwardRate>
<reverseRate>0.0196</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- Irreversible IC Ca Buffer Ca + CaB <-> CaBCa -->
<Reaction name = "CaIn_buffer" id="CaIn_buffer">
<Reactant specieID="Ca"/>
<Reactant specieID="CaB"/>
<Product specieID="CaBCa"/>
<forwardRate>2.8e-5</forwardRate>
<reverseRate>0</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--1A) CaM + 2Ca <-> CaMCa2C GQ RXN FILE, C or N can bind first-->
<Reaction name = "CaMC_bind" id="CaMC_bind">
<Reactant specieID="CaM"/>
<Reactant specieID="Ca" n="2"/>
<Product specieID="CaMCa2"/>
<forwardRate>0.006e-3</forwardRate>
<reverseRate>9.1e-3</reverseRate>
</Reaction>
<!--2A) CaMCa2C + 2Ca <-> CaMCa4 GQ RXN FILE, C or N can bind first-->
<Reaction name = "CaMCa2C_bind" id="CaMCa2C_bind">
<Reactant specieID="CaMCa2"/>
<Reactant specieID="Ca" n="2"/>
<Product specieID="CaMCa4"/>
<forwardRate>0.1e-3</forwardRate>
<reverseRate>1000e-3</reverseRate>
</Reaction>
<Reaction name = "NgCaM_bind" id="NgCaM_bind">
<Reactant specieID="CaM"/>
<Reactant specieID="Ng" />
<Product specieID="NgCaM"/>
<forwardRate>28.e-6</forwardRate>
<reverseRate>36.e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<Reaction name = "PP2_bind" id="PP2_bind">
<Reactant specieID="CaM"/>
<Reactant specieID="PP2B"/>
<Product specieID="PP2BCaM"/>
<forwardRate>4.6e-06</forwardRate>
<reverseRate>1.2e-6</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--4) CaMCa2 + PP2B <-> PP2BCaMCa2 -->
<Reaction name = "PP2CaMC2_bind" id="PP2CaMC2_bind">
<Reactant specieID="CaMCa2"/>
<Reactant specieID="PP2B"/>
<Product specieID="PP2BCaMCa2"/>
<forwardRate>4.6e-5</forwardRate>
<reverseRate>1.2e-6</reverseRate>
<!--
<forwardRate>1e-3</forwardRate>
<reverseRate>0.3e-3</reverseRate>
-->
<Q10>0.2</Q10>
</Reaction>
<!--5) CaMCa4 + PP2 <-> PP2B -->
<Reaction name = "PP2CaMCa4_bind" id="PP2CaMCa4_bind">
<Reactant specieID="CaMCa4"/>
<Reactant specieID="PP2B"/>
<Product specieID="PP2BCaMCa4"/>
<forwardRate>4.6e-5</forwardRate>
<reverseRate>1.2e-6</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--6) PP2BCaM + 2Ca <-> PP2BCaMCa2 -->
<Reaction name = "PP2CaMCa_bind" id="PP2CaMCa_bind">
<Reactant specieID="PP2BCaM"/>
<Reactant specieID="Ca" n="2"/>
<Product specieID="PP2BCaMCa2"/>
<forwardRate>6.e-4</forwardRate>
<reverseRate>9.1e-2</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--7) PP2CaMC2 + 2Ca <-> PP2B -->
<Reaction name = "PP2CaMCa2Ca_bind" id="PP2CaMCa2Ca_bind">
<Reactant specieID="PP2BCaMCa2"/>
<Reactant specieID="Ca" n="2"/>
<Product specieID="PP2BCaMCa4"/>
<forwardRate>0.0001</forwardRate>
<reverseRate>1</reverseRate>
<!--
<forwardRate>0.1e-3</forwardRate>
<reverseRate>10e-3</reverseRate>
-->
<Q10>0.2</Q10>
</Reaction>
<!--1) CaMCa4 + CK <-> CKCaMCa4 -->
<Reaction name = "CK bind" id="CK_bind">
<Reactant specieID="CaMCa4" />
<Reactant specieID="CK" />
<Product specieID="CKCaMCa4" />
<forwardRate> 0.02e-3 </forwardRate>
<reverseRate> 1.95e-3 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!--2a) 3 CKCaMCa4 + 1 CKCaMCa4 <-> 3 CKCaMCa4 + 1 CKpCaMCa4-->
<Reaction name = "CKCaM bind1" id="CKCaM_bind1">
<Reactant specieID="CKCaMCa4" power="4" />
<Product specieID="CKCaMCa4" power="3" />
<Product specieID="CKpCaMCa4" />
<forwardRate> 70.0e-18 </forwardRate>
<reverseRate> 0e-3 </reverseRate>
<Q10> 2 </Q10>
</Reaction>
<!--2b) 2 CKCaMCa4 + 1 CKCaMCa4 <-> 2 CKCaMCa4 + 1 CKpCaMCa4-->
<Reaction name = "CKCaM bind2" id="CKCaM_bind2">
<Reactant specieID="CKCaMCa4" power="3" />
<Product specieID="CKCaMCa4" power="2" />
<Product specieID="CKpCaMCa4" />
<forwardRate> 8.0e-12 </forwardRate>
<reverseRate> 0e-3 </reverseRate>
<Q10> 2 </Q10>
</Reaction>
<!--2c) 2 CKpCaMCa4 + 2 CKCaMCa4 <-> 3 CKpCaMCa4 + 1 CKCaMCa4-->
<Reaction name = "CKCaM bind3" id="CKCaM_bind3">
<Reactant specieID="CKpCaMCa4" power="2" />
<Reactant specieID="CKCaMCa4" power="2" />
<Product specieID="CKCaMCa4" />
<Product specieID="CKpCaMCa4" power="3" />
<forwardRate> 110.1e-18 </forwardRate>
<reverseRate> 0e-3 </reverseRate>
<Q10> 2 </Q10>
</Reaction>
<!-- CKpCaMCaMCa4 <-> CKp + CaMCa4 -->
<Reaction name = "CKp auto" id="CKp_auto">
<Reactant specieID="CKpCaMCa4" />
<Product specieID="CaMCa4" />
<Product specieID="CKp" />
<forwardRate> 0.001e-3 </forwardRate>
<reverseRate> 0.02e-3 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!-- CKp + PP1 <-> CKpPP1 -->
<Reaction name = "CKp bind" id="CKp_bind">
<Reactant specieID="CKp" />
<Reactant specieID="PP1" />
<Product specieID="CKpPP1" />
<forwardRate> 0.045e-06 </forwardRate>
<reverseRate> 0.8e-03 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!-- CKpPP1 -> PP1 + CK -->
<Reaction name = "CKpPP1 reac" id="CKpPP1_reac">
<Reactant specieID="CKpPP1" />
<Product specieID="PP1" />
<Product specieID="CK" />
<forwardRate> 0.01e-03 </forwardRate>
<reverseRate> 0.0 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!-- CKpCaMCa4 + PP1 <-> CKpCaMCa4PP1 -->
<Reaction name = "CKpCaMCa4PP1_bind" id="CKpCaMPP1_bind">
<Reactant specieID="CKpCaMCa4" />
<Reactant specieID="PP1" />
<Product specieID="CKpCaMCa4PP1" />
<forwardRate> 0.01e-06 </forwardRate>
<reverseRate> 0.9e-03 </reverseRate>
</Reaction>
<!--Dephos of CKpCaMCa4 by PP1 -->
<!-- CKpCaMCa4PP1 -> PP1 + CKCaMCa4 -->
<Reaction name = "CKpCaMCa4PP1_reac" id="CKpCaMPP1_reac">
<Reactant specieID="CKpCaMCa4PP1" />
<Product specieID="PP1" />
<Product specieID="CKCaMCa4" />
<forwardRate> 0.0045e-3 </forwardRate>
<reverseRate> 0.0 </reverseRate>
</Reaction>
<Reaction name = "CRTP_bind" id="CRTP_bind">
<Reactant specieID="CRT"/>
<Reactant specieID="CaER"/>
<Product specieID="CRTP"/>
<forwardRate>1e-6</forwardRate>
<reverseRate>0.001</reverseRate>
</Reaction>
<Reaction name = "IP3R+IP3->S100" id="IP3R+IP3->S100">
<Reactant specieID="IP3R" />
<Reactant specieID="IP3" />
<Product specieID="S100" />
<forwardRate> 400e-6 </forwardRate>
<reverseRate> 0.052 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<Reaction name = "S100+Ca->S101" id="S100+Ca->S101">
<Reactant specieID="S100" />
<Reactant specieID="Ca" />
<Product specieID="S101" />
<forwardRate> 0.2e-6 </forwardRate>
<reverseRate> 0.00028179999999999997 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<Reaction name = "S101->S001+IP3" id="S101->S001+IP3">
<Reactant specieID="S001" />
<Reactant specieID="IP3" />
<Product specieID="S101" />
<forwardRate>400e-6 </forwardRate>
<reverseRate> 0.37736000000000003 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<Reaction name = "IP3R+Ca->S001" id="IP3R+Ca->S001">
<Reactant specieID="IP3R" />
<Reactant specieID="Ca" />
<Product specieID="S001" />
<forwardRate> 0.2e-6 </forwardRate>
<reverseRate> 2.8899999999999998e-05 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!-- -->
<Reaction name = "S010+IP3->S110" id="S010+IP3->S110">
<Reactant specieID="S010" />
<Reactant specieID="IP3" />
<Product specieID="S110" />
<forwardRate> 400e-6 </forwardRate>
<reverseRate> 0.052 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<Reaction name = "S110+Ca->S111" id="S110+Ca->S111">
<Reactant specieID="S110" />
<Reactant specieID="Ca" />
<Product specieID="S111" />
<forwardRate> 0.2e-6 </forwardRate>
<reverseRate> 0.00028179999999999997 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<Reaction name = "S111->S011+IP3" id="S111->S011+IP3">
<Reactant specieID="S011" />
<Reactant specieID="IP3" />
<Product specieID="S111" />
<forwardRate>400e-6 </forwardRate>
<reverseRate> 0.37736000000000003 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<Reaction name = "S010+Ca->S011" id="S010+Ca->S011">
<Reactant specieID="S010" />
<Reactant specieID="Ca" />
<Product specieID="S011" />
<forwardRate> 0.2e-6 </forwardRate>
<reverseRate> 2.8899999999999998e-05 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!-- -->
<Reaction name = "IP3R+Ca->S010" id="IP3R+Ca->S010">
<Reactant specieID="IP3R" />
<Reactant specieID="Ca" />
<Product specieID="S010" />
<forwardRate> 20e-6 </forwardRate>
<reverseRate> 0.0016468000000000001 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<Reaction name = "S100+Ca->S110" id="S100+Ca->S110">
<Reactant specieID="S100" />
<Reactant specieID="Ca" />
<Product specieID="S110" />
<forwardRate> 20e-6 </forwardRate>
<reverseRate> 0.0016468000000000001 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<Reaction name = "S101+Ca->S111" id="S101+Ca->S111">
<Reactant specieID="S101" />
<Reactant specieID="Ca" />
<Product specieID="S111" />
<forwardRate> 20e-6 </forwardRate>
<reverseRate> 0.0016468000000000001 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<Reaction name = "S001+Ca->S011" id="S001+Ca->S011">
<Reactant specieID="S001" />
<Reactant specieID="Ca" />
<Product specieID="S011" />
<forwardRate> 20e-6 </forwardRate>
<reverseRate> 0.0016468000000000001 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<Reaction name = "EROutflux" id="EROutflux">
<Reactant specieID="S110" n="3" />
<Reactant specieID="CaER" />
<Product specieID="S110" n="3" />
<Product specieID="Ca" />
<forwardRate> 800e-7 </forwardRate>
<reverseRate> 0.0016468000000000001 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<Reaction name = "ACh+m1R-AChm1R" id="ACh+m1R-AChm1R">
<Reactant specieID="ACh" />
<Reactant specieID="m1R" />
<Product specieID="AChm1R" />
<forwardRate> 0.095e-06 </forwardRate>
<reverseRate> 2.5e-02 </reverseRate>
</Reaction>
<Reaction name = "Gqabg+AChm1R-AChm1RGq" id="Gqabg+AChm1R-AChm1RGq">
<Reactant specieID="Gqabg" />
<Reactant specieID="AChm1R" />
<Product specieID="AChm1RGq" />
<forwardRate> 0.024e-03 </forwardRate>
<reverseRate> 0.42e-03 </reverseRate>
</Reaction>
<Reaction name = "Gqabg+m1R- -m1RGq" id="Gqabg+m1R- -m1RGq">
<Reactant specieID="Gqabg" />
<Reactant specieID="m1R" />
<Product specieID="m1RGq" />
<forwardRate> 0.000576e-03 </forwardRate>
<reverseRate> 0.42e-03 </reverseRate>
</Reaction>
<Reaction name = "ACh+m1RGq- -AChm1RGq" id="ACh+m1RGq- -AChm1RGq">
<Reactant specieID="ACh" />
<Reactant specieID="m1RGq" />
<Product specieID="AChm1RGq" />
<forwardRate> 0.00396e-03 </forwardRate>
<reverseRate> 2.5e-02 </reverseRate>
</Reaction>
<Reaction name = "AChm1RGq-GqaGTP+AChm1RGbg" id="AChm1RGq-GqaGTP+AChm1RGbg">
<Reactant specieID="AChm1RGq" />
<Product specieID="GqaGTP" />
<Product specieID="AChm1R" />
<Product specieID="Gbg" />
<forwardRate> 0.5e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<Reaction name = "GqaGTP-GqaGDP" id="GqaGTP-GqaGDP">
<Reactant specieID="GqaGTP" />
<Product specieID="GqaGDP" />
<forwardRate> 1e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<Reaction name = "GqaGDP+Gbg-Gqabg" id="GqaGDP+Gbg-Gqabg">
<Reactant specieID="GqaGDP" />
<Reactant specieID="Gbg" />
<Product specieID="Gqabg" />
<forwardRate> 2e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<Reaction name = "Plc+Ca-PlcCa" id="Plc+Ca-PlcCa">
<Reactant specieID="Ca" />
<Reactant specieID="Plc" />
<Product specieID="PlcCa" />
<forwardRate> 0.0005e-03 </forwardRate>
<reverseRate> 1e-03 </reverseRate>
</Reaction>
<Reaction name = "PlcCa+GqaGTP-PlcCaGqa" id="PlcCa+GqaGTP-PlcCaGqa">
<Reactant specieID="GqaGTP" />
<Reactant specieID="PlcCa" />
<Product specieID="PlcCaGqa" />
<forwardRate> 0.0035e-03 </forwardRate>
<reverseRate> 0.7e-03 </reverseRate>
</Reaction>
<Reaction name = "Plc+GqaGTP-PlcGqa" id="Plc+GqaGTP-PlcGqa">
<Reactant specieID="GqaGTP" />
<Reactant specieID="Plc" />
<Product specieID="PlcGqa" />
<forwardRate> 0.0007e-03 </forwardRate>
<reverseRate> 0.7e-03 </reverseRate>
</Reaction>
<Reaction name = "PlcGaGTP+Ca-PlcCaGqa" id="PlcGaGTP+Ca-PlcCaGqa">
<Reactant specieID="Ca" />
<Reactant specieID="PlcGqa" />
<Product specieID="PlcCaGqa" />
<forwardRate> 0.0025e-03 </forwardRate>
<reverseRate> 1.0e-03 </reverseRate>
</Reaction>
<Reaction name = "PlcCa+Pip2-PlcCaPip2" id="PlcCa+Pip2-PlcCaPip2">
<Reactant specieID="PlcCa" />
<Reactant specieID="Pip2" />
<Product specieID="PlcCaPip2" />
<forwardRate> 0.05e-06 </forwardRate>
<reverseRate> 1.8e-03 </reverseRate>
</Reaction>
<Reaction name = "PlcCaPip2-PlcCa+Dag+IP3" id="PlcCaPip2-PlcCa+Dag+IP3">
<Reactant specieID="PlcCaPip2" />
<Product specieID="PlcCa" />
<Product specieID="IP3" />
<Product specieID="Dag" />
<forwardRate> 0.45e-03 </forwardRate>
<reverseRate> 0e-03 </reverseRate>
</Reaction>
<Reaction name = "PlcCaGqa+Pip2-PlcCaGqaPip2" id="PlcCaGqa+Pip2-PlcCaGqaPip2">
<Reactant specieID="PlcCaGqa" />
<Reactant specieID="Pip2" />
<Product specieID="PlcCaGqaPip2" />
<forwardRate> 1.665e-06 </forwardRate>
<reverseRate> 60e-03 </reverseRate>
</Reaction>
<Reaction name = "PlcCaGqaPip2-PlcCaGqaDag+IP3" id="PlcCaGqaPip2-PlcCaGqaDag+IP3">
<Reactant specieID="PlcCaGqaPip2" />
<Product specieID="PlcCaGqa" />
<Product specieID="Dag" />
<Product specieID="IP3" />
<forwardRate> 30e-03 </forwardRate>
<reverseRate> 0e-03 </reverseRate>
</Reaction>
<Reaction name = "PlcGqa-Plc+GqaGDP" id="PlcGqa-Plc+GqaGDP">
<Reactant specieID="PlcGqa" />
<Product specieID="Plc" />
<Product specieID="GqaGDP" />
<forwardRate> 12e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<Reaction name = "PlcCaGqa-PlcCa+GaGDP" id="PlcCaGqa-Plc+GaGDP">
<Reactant specieID="PlcCaGqa" />
<Product specieID="PlcCa" />
<Product specieID="GqaGDP" />
<forwardRate> 12e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
</Reaction>
<Reaction name = "IP3-IP3degrad" id="IP3-IP3degrad"> -->
<Reactant specieID="IP3" />
<Product specieID="IP3degrad" />
<forwardRate> 0.33e-03 </forwardRate>
<reverseRate> 0.0e-03 </reverseRate>
</Reaction>
<Reaction name = "IP3degrad+PIkinase-IP3degPIk" id="PIkinase1">
<Reactant specieID="IP3degrad" />
<Reactant specieID="PIkinase" />
<Product specieID="IP3degPIk" />
<forwardRate> 0.0005e-3 </forwardRate>
<reverseRate> 0.4e-03 </reverseRate>
</Reaction>
<Reaction name = "IP3degPIk-PIP2 + PIkinase" id="PIkinase2">
<Reactant specieID="IP3degPIk" />
<Product specieID="PIkinase" />
<Product specieID="Pip2" />
<forwardRate> 0.1e-3 </forwardRate>
<reverseRate> 0e-3 </reverseRate>
</Reaction>
<!-- 8) AC8 + CaMCa4 <-> AC8CaM -->
<Reaction name = "AC8_CaMCa4_bind" id="AC8_CaMCa4_bind">
<Reactant specieID="AC8"/>
<Reactant specieID="CaMCa4"/>
<Product specieID="AC8CaMCa4"/>
<forwardRate>0.00125e-3</forwardRate>
<reverseRate>1e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- 9) AC8CaM + ATP <-> AC8CaMATP -->
<Reaction name = "AC8CaMCa4_ATP_bind" id="AC8CaMCa4_ATP_bind">
<Reactant specieID="AC8CaMCa4"/>
<!--<Reactant specieID="ATP"/>-->
<Product specieID="AC8CaMCa4ATP"/>
<forwardRate>20</forwardRate>
<reverseRate>2273e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- 10) AC8CaMATP -> AC8CaM + cAMP -->
<Reaction name = "AC8CaMCa4ATP_disso" id="AC8CaMCa4ATP_disso">
<Reactant specieID="AC8CaMCa4ATP"/>
<Product specieID="cAMP"/>
<Product specieID="AC8CaMCa4"/>
<forwardRate>28.e-3</forwardRate>
<reverseRate>0</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--1) PKA + 2cAMP <-> PKAcAMP2 -->
<Reaction name="PKA_bind" id="PKA_bind">
<Reactant specieID="PKA"/>
<Reactant specieID="cAMP" n="2"/>
<Product specieID="PKAcAMP2"/>
<forwardRate>2.60868e-07</forwardRate>
<reverseRate>6.0e-05</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--2) PKAcAMP2 + 2cAMP <-> PKAcAMP4 -->
<Reaction name="PKAcAMP2_bind" id="PKAcAMP2_bind">
<Reactant specieID="PKAcAMP2"/>
<Reactant specieID="cAMP" n="2"/>
<Product specieID="PKAcAMP4"/>
<forwardRate>3.46218e-07</forwardRate>
<reverseRate>0.0006</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--1) Epac1-camps + cAMP <-> Epac1-camps_cAMP -->
<Reaction name = "Epac_camps_cAMP_bind" id="Epac_camps_cAMP_bind">
<Reactant specieID="Epac1"/>
<Reactant specieID="cAMP"/>
<Product specieID="Epac1cAMP"/>
<forwardRate>0.031e-6</forwardRate>
<reverseRate>6.51e-05</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- Inhibitor 1 Phospho and Dephosphorylation -->
<!-- Hemmings et al J Biol Chem 259 14491-->
<!--1) I1 + PKAc <-> I1PKAc -->
<Reaction name = "I1_bind" id="I1_bind">
<Reactant specieID="I1"/>
<Reactant specieID="PKAc"/>
<Product specieID="I1PKAc"/>
<forwardRate>0.0014e-3</forwardRate>
<reverseRate>0.0056</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--2) I1PKAc -> Ip35 + PKAc: default kb=0 -->
<Reaction name = "I1PKAc_reac" id="I1PKAc_reac">
<Reactant specieID="I1PKAc"/>
<Product specieID="Ip35"/>
<Product specieID="PKAc"/>
<forwardRate>1.4e-3</forwardRate>
<reverseRate>0</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--3) Ip35 + PP1 <-> Ip35pp1 -->
<Reaction name = "Ip35_bind" id="Ip35_bind">
<Reactant specieID="Ip35"/>
<Reactant specieID="PP1"/>
<Product specieID="Ip35PP1"/>
<forwardRate>0.001e-3</forwardRate>
<reverseRate>0.0011e-3</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--4) Ip35 + PP2B <-> Ip35pp2b -->
<Reaction name = "Ip35pp2b_bind" id="Ip35pp2b_bind">
<Reactant specieID="Ip35"/>
<Reactant specieID="PP2BCaMCa4"/>
<Product specieID="Ip35PP2BCaMCa4"/>
<forwardRate>9.625e-05</forwardRate>
<reverseRate>0.33</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--5) Ip35pp2b -> I1 + PP2B -->
<Reaction name = "Ip35pp2b_reac" id="Ip35pp2b_reac">
<Reactant specieID="Ip35PP2BCaMCa4"/>
<Product specieID="I1"/>
<Product specieID="PP2BCaMCa4"/>
<forwardRate>0.055</forwardRate>
<reverseRate>0</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--6) Ip35pp1 + PP2B <-> Ip35p1p2 -->
<Reaction name = "Ip35pp1_bind" id="Ip35pp1_bind">
<Reactant specieID="Ip35PP1"/>
<Reactant specieID="PP2BCaMCa4"/>
<Product specieID="Ip35PP1PP2BCaMCa4"/>
<forwardRate>9.625e-5</forwardRate>
<reverseRate>0.33</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!--7a) Ip35p1p2 -> I1 + PP1PP2B -->
<Reaction name = "Ip35p1p2_reac" id="Ip35p1p2_reac">
<Reactant specieID="Ip35PP1PP2BCaMCa4"/>
<Product specieID="I1"/>
<Product specieID="PP1"/>
<Product specieID="PP2BCaMCa4"/>
<forwardRate>0.055</forwardRate>
<reverseRate>0</reverseRate>
<Q10>0.2</Q10>
</Reaction>
<!-- 07) cAMP + PDE4 <-> PDE4cAMP -->
<Reaction name = "PDE4 enzyme1" id="PDE4bind">
<Reactant specieID="PDE4" />
<Reactant specieID="cAMP" />
<Product specieID="PDE4cAMP" />
<forwardRate> 0.02166e-03 </forwardRate>
<reverseRate> 68.950e-03 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!-- 08) PDE4cAMP -> AMP + PDE4 -->
<Reaction name = "PDE4 actvcomp" id="PDE4cat">
<Reactant specieID="PDE4cAMP" />
<Product specieID="PDE4" />
<forwardRate> 17.233e-03 </forwardRate>
<reverseRate> 0 </reverseRate>
<Q10> 0.2 </Q10>
</Reaction>
<!-- 09) PKAc + PDE4 -> PKAcPDE4 -->
<Reaction name = "PDE4 phosp1" id="phospPDE41">
<Reactant specieID="PKAc" />
<Reactant specieID="PDE4" />
<Product specieID="PKAcPDE4" />