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This CellML file was generated on 17/12/2009 at 8:45:41 at a.m. using:
COR (0.9.31.1351)
Copyright 2002-2009 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 role for calcium release-activated current (CRAC) in cholinergic modulation of electrical activity in pancreatic beta-cells</title>
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<para> This model runs in both COR and PCEnv to reproduce the figures shown in the original paper. The units have been checked and they are consistent.</para>
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<para>ABSTRACT: S. Bordin and colleagues have proposed that the depolarizing effects of acetylcholine and other muscarinic agonists on pancreatic beta-cells are mediated by a calcium release-activated current (CRAC). We support this hypothesis with additional data, and present a theoretical model which accounts for most known data on muscarinic effects. Additional phenomena, such as the biphasic responses of beta-cells to changes in glucose concentration and the depolarizing effects of the sarco-endoplasmic reticulum calcium ATPase pump poison thapsigargin, are also accounted for by our model. The ability of this single hypothesis, that CRAC is present in beta-cells, to explain so many phenomena motivates a more complete characterization of this current.
</para>
<para>The complete paper reference is cited below:</para>
<para>A Role for Calcium Release-Activated Current (CRAC) in Cholinergic Modulation of Electrical Activity in Pancreatic Beta-Cells, Richard Bertram, Paul Smolen, Arthur Sherman, David Mears, Illani Atwater, Franz Martin and Bernat Soria, 1995,
<emphasis>Biophysical Journal</emphasis>, 68, 2323-2332. <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/7647236">PubMed ID: 7647236</ulink>
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<Orgname xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">The University of Auckland</Orgname>
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<rdf:value xml:lang="en">This is the CellML description of Bertram et al's 1995 model for a modulatory role for CRAC in islet electrical activity.</rdf:value>
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<Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Lloyd</Family>
<Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Catherine</Given>
<Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">May</Other>
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</rdf:RDF> <units name="millisecond">
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<units name="per_millisecond">
<unit exponent="-1" units="millisecond"/>
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<units name="per_micromolar">
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<units name="micromolar_per_millisecond">
<unit units="micromolar"/>
<unit exponent="-1" units="millisecond"/>
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<units name="micromolar_per_millisecond_picoA">
<unit units="micromolar"/>
<unit exponent="-1" units="millisecond"/>
<unit exponent="-1" units="picoA"/>
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<units name="millivolt">
<unit prefix="milli" units="volt"/>
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<units name="micromolar">
<unit prefix="micro" units="mole"/>
<unit exponent="-1" units="litre"/>
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<units name="micrometer_3">
<unit exponent="3" prefix="micro" units="meter"/>
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<unit prefix="pico" units="siemens"/>
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<units name="picoA">
<unit prefix="pico" units="ampere"/>
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<units name="femtoF">
<unit prefix="femto" units="farad"/>
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<component name="environment">
<variable cmeta:id="environment_time" name="time" public_interface="out" units="millisecond"/>
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<component name="membrane">
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<variable initial_value="6158" name="Cm" units="femtoF"/>
<variable name="time" public_interface="in" units="millisecond"/>
<variable name="i_K" public_interface="in" units="picoA"/>
<variable name="i_K_Ca" public_interface="in" units="picoA"/>
<variable name="i_K_ATP" public_interface="in" units="picoA"/>
<variable name="i_CRAC" public_interface="in" units="picoA"/>
<variable name="i_Ca" public_interface="in" units="picoA"/>
<variable name="i_leak" public_interface="in" units="picoA"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
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<ci>time</ci>
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<divide/>
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<minus/>
<apply>
<plus/>
<ci>i_Ca</ci>
<ci>i_K</ci>
<ci>i_K_ATP</ci>
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</apply>
<ci>Cm</ci>
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</math>
</component>
<component name="K_current">
<variable name="time" private_interface="out" public_interface="in" units="millisecond"/>
<variable cmeta:id="K_current_i_K" name="i_K" public_interface="out" units="picoA"/>
<variable initial_value="-70" name="V_K" public_interface="out" units="millivolt"/>
<variable initial_value="3900" name="g_K" units="picoS"/>
<variable name="V" private_interface="out" public_interface="in" units="millivolt"/>
<variable name="n" private_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_K</ci>
<apply>
<times/>
<ci>g_K</ci>
<ci>n</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>V_K</ci>
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</apply>
</apply>
</math>
</component>
<component name="K_channel_n_gate">
<variable initial_value="0.0005" name="n" public_interface="out" units="dimensionless"/>
<variable name="n_infinity" units="dimensionless"/>
<variable name="tau_n" units="millisecond"/>
<variable initial_value="-15" name="Vn" units="millivolt"/>
<variable initial_value="6" name="Sn" units="millivolt"/>
<variable initial_value="1.85" name="lambda_n" units="dimensionless"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="millisecond"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
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<ci>n</ci>
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<apply>
<divide/>
<apply>
<times/>
<ci>lambda_n</ci>
<apply>
<minus/>
<ci>n_infinity</ci>
<ci>n</ci>
</apply>
</apply>
<ci>tau_n</ci>
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</apply>
<apply>
<eq/>
<ci>n_infinity</ci>
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<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci>Vn</ci>
<ci>V</ci>
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<ci>Sn</ci>
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</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>tau_n</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millisecond">9.09</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci>V</ci>
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<ci>Sn</ci>
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</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="K_ATP_current">
<variable cmeta:id="K_ATP_current_i_K_ATP" name="i_K_ATP" public_interface="out" units="picoA"/>
<variable initial_value="150" name="g_K_ATP" units="picoS"/>
<variable name="V_K" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="millisecond"/>
<variable name="V" public_interface="in" units="millivolt"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_K_ATP</ci>
<apply>
<times/>
<ci>g_K_ATP</ci>
<apply>
<minus/>
<ci>V</ci>
<ci>V_K</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="fast_Ca_current">
<variable cmeta:id="fast_Ca_current_i_Ca_f" name="i_Ca_f" public_interface="out" units="picoA"/>
<variable initial_value="100" name="V_Ca" public_interface="out" units="millivolt"/>
<variable initial_value="810" name="g_Ca_f" units="picoS"/>
<variable name="time" public_interface="in" units="millisecond"/>
<variable name="V" private_interface="out" public_interface="in" units="millivolt"/>
<variable name="m_f_infinity" private_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_Ca_f</ci>
<apply>
<times/>
<ci>g_Ca_f</ci>
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<apply>
<minus/>
<ci>V</ci>
<ci>V_Ca</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="fast_Ca_channel_m_gate">
<variable name="m_f_infinity" public_interface="out" units="dimensionless"/>
<variable initial_value="-20" name="Vm_f" units="millivolt"/>
<variable initial_value="7.5" name="Sm_f" units="millivolt"/>
<variable name="V" public_interface="in" units="millivolt"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>m_f_infinity</ci>
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<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci>Vm_f</ci>
<ci>V</ci>
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<ci>Sm_f</ci>
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</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="slow_Ca_current">
<variable cmeta:id="slow_Ca_current_i_Ca_s" name="i_Ca_s" public_interface="out" units="picoA"/>
<variable initial_value="510" name="g_Ca_s" units="picoS"/>
<variable name="time" private_interface="out" public_interface="in" units="millisecond"/>
<variable name="V" private_interface="out" public_interface="in" units="millivolt"/>
<variable name="V_Ca" public_interface="in" units="millivolt"/>
<variable name="m_s_infinity" private_interface="in" units="dimensionless"/>
<variable name="jm" private_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>i_Ca_s</ci>
<apply>
<times/>
<ci>g_Ca_s</ci>
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<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<ci>jm</ci>
</apply>
<apply>
<minus/>
<ci>V</ci>
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</apply>
</apply>
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</component>
<component name="slow_Ca_channel_m_gate">
<variable name="m_s_infinity" public_interface="out" units="dimensionless"/>
<variable initial_value="-16" name="Vm_s" units="millivolt"/>
<variable initial_value="10" name="Sm_s" units="millivolt"/>
<variable name="V" public_interface="in" units="millivolt"/>
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<eq/>
<ci>m_s_infinity</ci>
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<plus/>
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</math>
</component>
<component name="slow_Ca_channel_j_gate">
<variable initial_value="0.12" name="jm" public_interface="out" units="dimensionless"/>
<variable name="j" units="dimensionless"/>
<variable name="jm_infinity" units="dimensionless"/>
<variable initial_value="-53" name="Vj" units="millivolt"/>
<variable name="tau_j" units="millisecond"/>
<variable initial_value="2" name="Sj" units="millivolt"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="time" public_interface="in" units="millisecond"/>
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<ci>j</ci>
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<minus/>
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<ci>V</ci>
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<ci>Sj</ci>
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<apply>
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<ci>tau_j</ci>
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<plus/>
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<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millisecond">50000</cn>
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<plus/>
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<minus/>
<ci>V</ci>
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<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">4</cn>
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<apply>
<exp/>
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<minus/>
<ci>Vj</ci>
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<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millivolt">4</cn>
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<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="millisecond">1500</cn>
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<divide/>
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<minus/>
<ci>jm_infinity</ci>
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</component>
<component name="Ca_current_total">
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<variable name="i_Ca_f" public_interface="in" units="picoA"/>
<variable name="i_Ca_s" public_interface="in" units="picoA"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
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<eq/>
<ci>i_Ca</ci>
<apply>
<plus/>
<ci>i_Ca_f</ci>
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</component>
<component name="K_Ca_current">
<variable cmeta:id="K_Ca_current_i_K_Ca" name="i_K_Ca" public_interface="out" units="picoA"/>
<variable initial_value="1200" name="g_K_Ca" units="picoS"/>
<variable name="time" public_interface="in" units="millisecond"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="V_K" public_interface="in" units="millivolt"/>
<variable name="Ca_i" public_interface="in" units="micromolar"/>
<variable initial_value="0.55" name="kdkca" units="micromolar"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
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<ci>i_K_Ca</ci>
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<power/>
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<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">5</cn>
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<apply>
<plus/>
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<ci>Ca_i</ci>
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<power/>
<ci>kdkca</ci>
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<apply>
<minus/>
<ci>V</ci>
<ci>V_K</ci>
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<component name="CRAC_current">
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<variable initial_value="75" name="g_CRAC" units="picoS"/>
<variable initial_value="0" name="V_CRAC" public_interface="out" units="millivolt"/>
<variable name="time" public_interface="in" units="millisecond"/>
<variable name="V" public_interface="in" units="millivolt"/>
<variable name="Ca_er" private_interface="out" public_interface="in" units="micromolar"/>
<variable name="r_infinity" private_interface="in" units="dimensionless"/>
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<variable name="Ca_er" public_interface="in" units="micromolar"/>
<variable initial_value="3" name="Ca_er_bar" units="micromolar"/>
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<component name="leak_current">
<variable name="i_leak" public_interface="out" units="picoA"/>
<variable initial_value="0" name="g_leak" units="picoS"/>
<variable name="V_CRAC" public_interface="in" units="millivolt"/>
<variable name="time" private_interface="out" public_interface="in" units="millisecond"/>
<variable name="V" private_interface="out" public_interface="in" units="millivolt"/>
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<component name="ER_parameters">
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<variable name="Ca_i" public_interface="in" units="micromolar"/>
<variable cmeta:id="ER_parameters_J_er_p" name="J_er_p" public_interface="out" units="micromolar_per_millisecond"/>
<variable initial_value="0" name="IP3" units="micromolar"/>
<variable initial_value="0.1" name="kerp" units="micromolar"/>
<variable initial_value="0.24" name="verp" units="micromolar_per_millisecond"/>
<variable initial_value="0.1" name="dact" units="micromolar"/>
<variable initial_value="0.4" name="dinh" units="micromolar"/>
<variable initial_value="0.2" name="dip3" units="micromolar"/>
<variable name="a_infinity" units="dimensionless"/>
<variable name="b_infinity" units="dimensionless"/>
<variable name="h_infinity" units="dimensionless"/>
<variable name="O" public_interface="out" units="per_millisecond"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
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<eq/>
<ci>b_infinity</ci>
<apply>
<divide/>
<ci>IP3</ci>
<apply>
<plus/>
<ci>IP3</ci>
<ci>dip3</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>h_infinity</ci>
<apply>
<divide/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<plus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<apply>
<divide/>
<ci>Ca_i</ci>
<ci>dinh</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>O</ci>
<apply>
<times/>
<apply>
<power/>
<ci>a_infinity</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
</apply>
<apply>
<power/>
<ci>b_infinity</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
</apply>
<apply>
<power/>
<ci>h_infinity</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_millisecond">1</cn>
</apply>
</apply>
</math>
</component>
<component name="Ca_equations">
<variable name="time" private_interface="out" public_interface="in" units="millisecond"/>
<variable initial_value="9" name="Ca_er" public_interface="out" units="micromolar"/>
<variable initial_value="0.11" name="Ca_i" private_interface="out" public_interface="out" units="micromolar"/>
<variable name="J_er_tot" public_interface="out" units="micromolar_per_millisecond"/>
<variable name="J_er_p" private_interface="in" units="micromolar_per_millisecond"/>
<variable name="J_er_IP3" units="micromolar_per_millisecond"/>
<variable name="J_er_leak" units="micromolar_per_millisecond"/>
<variable name="J_mem_tot" public_interface="in" units="micromolar_per_millisecond"/>
<variable name="O" private_interface="in" units="per_millisecond"/>
<variable initial_value="0.02" name="perl" units="per_millisecond"/>
<variable initial_value="250" name="lambda_er" units="dimensionless"/>
<variable initial_value="5" name="sigma_er" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>J_er_tot</ci>
<apply>
<minus/>
<apply>
<plus/>
<ci>J_er_leak</ci>
<ci>J_er_IP3</ci>
</apply>
<ci>J_er_p</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>J_er_leak</ci>
<apply>
<times/>
<ci>perl</ci>
<apply>
<minus/>
<ci>Ca_er</ci>
<ci>Ca_i</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>J_er_IP3</ci>
<apply>
<times/>
<ci>O</ci>
<apply>
<minus/>
<ci>Ca_er</ci>
<ci>Ca_i</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_er</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>J_er_tot</ci>
</apply>
<apply>
<times/>
<ci>lambda_er</ci>
<ci>sigma_er</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Ca_i</ci>
</apply>
<apply>
<plus/>
<apply>
<divide/>
<ci>J_er_tot</ci>
<ci>lambda_er</ci>
</apply>
<ci>J_mem_tot</ci>
</apply>
</apply>
</math>
</component>
<component name="Ca_membrane_flux">
<variable name="time" public_interface="in" units="millisecond"/>
<variable initial_value="0.07" name="k_Ca" units="per_millisecond"/>
<variable initial_value="0.000003607" name="gamma" units="micromolar_per_millisecond_picoA"/>
<variable name="i_Ca" public_interface="in" units="picoA"/>
<variable name="Ca_i" public_interface="in" units="micromolar"/>
<variable name="J_mem_tot" public_interface="out" units="micromolar_per_millisecond"/>
<variable initial_value="0.01" name="f" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>J_mem_tot</ci>
<apply>
<times/>
<apply>
<minus/>
<ci>f</ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>gamma</ci>
<ci>i_Ca</ci>
</apply>
<apply>
<times/>
<ci>k_Ca</ci>
<ci>Ca_i</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<group>
<relationship_ref relationship="encapsulation"/>
<component_ref component="K_current">
<component_ref component="K_channel_n_gate"/>
</component_ref>
<component_ref component="fast_Ca_current">
<component_ref component="fast_Ca_channel_m_gate"/>
</component_ref>
<component_ref component="slow_Ca_current">
<component_ref component="slow_Ca_channel_m_gate"/>
<component_ref component="slow_Ca_channel_j_gate"/>
</component_ref>
<component_ref component="CRAC_current">
<component_ref component="CRAC_r_gate"/>
</component_ref>
<component_ref component="Ca_equations">
<component_ref component="ER_parameters"/>
</component_ref>
</group>
<connection>
<map_components component_1="membrane" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="K_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="K_ATP_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="fast_Ca_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="slow_Ca_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="K_Ca_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="CRAC_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Ca_equations" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Ca_membrane_flux" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="leak_current" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="K_current" component_2="membrane"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_K" variable_2="i_K"/>
</connection>
<connection>
<map_components component_1="K_ATP_current" component_2="membrane"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_K_ATP" variable_2="i_K_ATP"/>
</connection>
<connection>
<map_components component_1="fast_Ca_current" component_2="membrane"/>
<map_variables variable_1="V" variable_2="V"/>
</connection>
<connection>
<map_components component_1="slow_Ca_current" component_2="membrane"/>
<map_variables variable_1="V" variable_2="V"/>
</connection>
<connection>
<map_components component_1="K_Ca_current" component_2="membrane"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_K_Ca" variable_2="i_K_Ca"/>
</connection>
<connection>
<map_components component_1="CRAC_current" component_2="membrane"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_CRAC" variable_2="i_CRAC"/>
</connection>
<connection>
<map_components component_1="leak_current" component_2="membrane"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="i_leak" variable_2="i_leak"/>
</connection>
<connection>
<map_components component_1="K_current" component_2="K_ATP_current"/>
<map_variables variable_1="V_K" variable_2="V_K"/>
</connection>
<connection>
<map_components component_1="K_current" component_2="K_Ca_current"/>
<map_variables variable_1="V_K" variable_2="V_K"/>
</connection>
<connection>
<map_components component_1="fast_Ca_current" component_2="slow_Ca_current"/>
<map_variables variable_1="V_Ca" variable_2="V_Ca"/>
</connection>
<connection>
<map_components component_1="slow_Ca_current" component_2="Ca_current_total"/>
<map_variables variable_1="i_Ca_s" variable_2="i_Ca_s"/>
</connection>
<connection>
<map_components component_1="fast_Ca_current" component_2="Ca_current_total"/>
<map_variables variable_1="i_Ca_f" variable_2="i_Ca_f"/>
</connection>
<connection>
<map_components component_1="Ca_current_total" component_2="membrane"/>
<map_variables variable_1="i_Ca" variable_2="i_Ca"/>
</connection>
<connection>
<map_components component_1="Ca_current_total" component_2="Ca_membrane_flux"/>
<map_variables variable_1="i_Ca" variable_2="i_Ca"/>
</connection>
<connection>
<map_components component_1="CRAC_current" component_2="Ca_equations"/>
<map_variables variable_1="Ca_er" variable_2="Ca_er"/>
</connection>
<connection>
<map_components component_1="K_Ca_current" component_2="Ca_equations"/>
<map_variables variable_1="Ca_i" variable_2="Ca_i"/>
</connection>
<connection>
<map_components component_1="CRAC_current" component_2="leak_current"/>
<map_variables variable_1="V_CRAC" variable_2="V_CRAC"/>
</connection>
<connection>
<map_components component_1="Ca_equations" component_2="Ca_membrane_flux"/>
<map_variables variable_1="Ca_i" variable_2="Ca_i"/>
<map_variables variable_1="J_mem_tot" variable_2="J_mem_tot"/>
</connection>
<connection>
<map_components component_1="ER_parameters" component_2="Ca_equations"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="Ca_i" variable_2="Ca_i"/>
<map_variables variable_1="J_er_p" variable_2="J_er_p"/>
<map_variables variable_1="O" variable_2="O"/>
</connection>
<connection>
<map_components component_1="K_current" component_2="K_channel_n_gate"/>
<map_variables variable_1="n" variable_2="n"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="V" variable_2="V"/>
</connection>
<connection>
<map_components component_1="fast_Ca_current" component_2="fast_Ca_channel_m_gate"/>
<map_variables variable_1="m_f_infinity" variable_2="m_f_infinity"/>
<map_variables variable_1="V" variable_2="V"/>
</connection>
<connection>
<map_components component_1="slow_Ca_current" component_2="slow_Ca_channel_m_gate"/>
<map_variables variable_1="V" variable_2="V"/>
<map_variables variable_1="m_s_infinity" variable_2="m_s_infinity"/>
</connection>
<connection>
<map_components component_1="slow_Ca_current" component_2="slow_Ca_channel_j_gate"/>
<map_variables variable_1="jm" variable_2="jm"/>
<map_variables variable_1="time" variable_2="time"/>
<map_variables variable_1="V" variable_2="V"/>
</connection>
<connection>
<map_components component_1="CRAC_current" component_2="CRAC_r_gate"/>
<map_variables variable_1="r_infinity" variable_2="r_infinity"/>
<map_variables variable_1="Ca_er" variable_2="Ca_er"/>
</connection>
</model>
