- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2009-06-17 16:21:29+12:00
- Desc:
- committing version01 of warashina_ogura_2004
- Permanent Source URI:
- https://models.cellml.org/workspace/warashina_ogura_2004/rawfile/0084a08956b59d8e17535af20ef5aad3bfff4b67/warashina_ogura_2004.cellml
<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : warashina_model_2004.xml
CREATED : 3rd February 2004
LAST MODIFIED : 27th April 2005
AUTHOR : Catherine Lloyd
Bioengineering Instute
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.0 Specification released on
10th August 2001, and the 16/01/2002 CellML Metadata 1.0 Specification.
DESCRIPTION : This file contains a CellML description of Warashina and Ogura's 2004 mathematical model of stimulation-secretion coupling in a chromaffin cell.
CHANGES:
27/04/2005 - PJV - Made MathML id's unique. Changed unit dimension
to correct inconsistancy. Removed undefined
initial values.
--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" cmeta:id="warashina_ogura_2004_version01" name="warashina_ogura_2004_version01">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Modelling Stimulation-Sectretion Coupling in a Chromaffin Cell</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This is the original unchecked version of the model imported from the previous
CellML model repository, 24-Jan-2006.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
Adrenal chromaffin cells have been used extensively for studying the mechanisms involved in stimulation-secretion coupling, namely electrophysiological progesses, signal transduction pathways, calcium homeostasis, and exocytotic processes. However, despite the accululation of large quantities of experimental data, a clear understanding of how these processes interact is lacking. In the Warashina and Ogura 2004 publication described here, the authors present a mathematical model which describes a chromaffin cell (see the figure below). This model is able to simulate the cell's secretory responses, including the process of stimulation-secretion coupling.
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
<ulink url="http://springerlink.metapress.com/app/home/contribution.asp?wasp=acecbdaqwg6yph41qjft&referrer=parent&backto=issue,5,16;journal,5,110;linkingpublicationresults,1:100448,1">Modeling of stimulation-secretion coupling in a chromaffin cell</ulink>, A. Warashina and T. Ogura, 2004, <ulink url="http://www.springerlink.com/app/home/journal.asp?wasp=g2e72bwqwj3txlfgxldv&referrer=backto&backto=searchpublicationsresults,3,3;&absoluteposition=1#A1">
<emphasis>European Journal of Physiology</emphasis>
</ulink>, 448, 369-391. (<ulink url="http://springerlink.metapress.com/media/988TNJWHWL5HJFH4UC5V/Contributions/F/B/A/4/FBA4F5TX6P4PEC61_html/fulltext.html">A Full text (HTML)</ulink> and PDF versions of the article are available to subscribers on the <emphasis>European Journal of Physiology</emphasis> website. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14730449&dopt=Abstract">PubMed ID: 14730449</ulink>
</para>
<informalfigure float="0" id="fig_cell_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>cell diagram</title>
</objectinfo>
<imagedata fileref="warashina_2004.png"/>
</imageobject>
</mediaobject>
<caption>The model chromaffin cell includes mechanisms involved in the excitatory synapse, Hodgkin-Huxley type Na<superscript>+</superscript> and K<superscript>+</superscript> channels, volatage-dependent Ca<superscript>2+</superscript> channels, Ca<superscript>2+</superscript>-dependent K<superscript>+</superscript> channels, Ca<superscript>2+</superscript> extrusion, buffered diffusion of intracellular Ca<superscript>2+</superscript>, Ca<superscript>2+</superscript> indication with a fluorescent dye, and Ca<superscript>2+</superscript>-triggered secretion.</caption>
</informalfigure>
<para>
Model simulations were carried out using the <ulink url="http://www.neuron.yale.edu/">NEURON</ulink> simulation environment. The simulations were able to reproduce several of the experimental results reported in the literature.
</para>
</sect1>
</article>
</documentation>
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</component>
<component name="membrane">
<variable units="millivolt" public_interface="out" name="V"/>
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<variable units="millisecond" name="tau2" initial_value="6.3"/>
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<component name="sodium_channel">
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<apply>
<minus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci> V </ci>
<cn cellml:units="millivolt"> 2.0 </cn>
</apply>
<cn cellml:units="millivolt"> 8.0 </cn>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="calcium_channel_m_gate_dm_dt">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> m </ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci> alpha_m </ci>
<apply>
<minus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> m </ci>
</apply>
</apply>
<apply>
<times/>
<ci> beta_m </ci>
<ci> m </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="calcium_channel_h_gate">
<variable units="dimensionless" public_interface="out" name="h"/>
<variable units="dimensionless" name="Fr"/>
<variable units="dimensionless" name="Ff" initial_value="0.79"/>
<variable units="dimensionless" name="Fm" initial_value="0.0"/>
<variable units="dimensionless" name="Fs" initial_value="0.0"/>
<variable units="millisecond" name="tau_f" initial_value="500.0"/>
<variable units="millisecond" name="tau_m"/>
<variable units="millisecond" name="tau_s"/>
<variable units="millisecond" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="h_calculation">
<eq/>
<ci> h </ci>
<apply>
<plus/>
<apply>
<times/>
<ci> Ff </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci> time </ci>
</apply>
<ci> tau_f </ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci> Fm </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci> time </ci>
</apply>
<ci> tau_m </ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci> Fs </ci>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci> time </ci>
</apply>
<ci> tau_s </ci>
</apply>
</apply>
</apply>
<ci> Fr </ci>
</apply>
</apply>
</math>
</component>
<component name="calcium_dependent_potassium_channel">
<variable units="microA_per_cm2" public_interface="out" name="i_SK"/>
<variable units="milliS_per_cm2" name="g_SK" initial_value="3.0"/>
<variable units="millisecond" public_interface="in" private_interface="out" name="time"/>
<variable units="millivolt" public_interface="in" private_interface="out" name="V"/>
<variable units="millimolar" public_interface="in" private_interface="out" name="Ca0"/>
<variable units="millivolt" public_interface="in" name="E_K"/>
<variable units="dimensionless" private_interface="in" name="m"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="i_SK_calculation">
<eq/>
<ci> i_SK </ci>
<apply>
<times/>
<ci> g_SK </ci>
<apply>
<power/>
<ci> m </ci>
<cn cellml:units="dimensionless"> 2.0 </cn>
</apply>
<apply>
<minus/>
<ci> V </ci>
<ci> E_K </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="calcium_dependent_potassium_channel_m_gate">
<variable units="dimensionless" public_interface="out" name="m"/>
<variable units="dimensionless" name="m_infinity"/>
<variable units="metre_per_second" name="beta_k" initial_value="0.1"/>
<variable units="dimensionless" name="n_SK" initial_value="1.7"/>
<variable units="millisecond" name="tau_m"/>
<variable units="millimolar" name="Car"/>
<variable units="nanomolar" name="Cac" initial_value="700.0"/>
<variable units="millimolar" public_interface="in" name="Ca0"/>
<variable units="millisecond" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="m_infinity_calculation">
<eq/>
<ci> m_infinity </ci>
<apply>
<divide/>
<ci> Car </ci>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> Car </ci>
</apply>
</apply>
</apply>
<apply id="tau_m_calculation">
<eq/>
<ci> tau_m </ci>
<apply>
<divide/>
<cn cellml:units="millisecond"> 1.0 </cn>
<apply>
<times/>
<ci> beta_k </ci>
<apply>
<plus/>
<cn cellml:units="millimolar"> 1.0 </cn>
<ci> Car </ci>
</apply>
</apply>
</apply>
</apply>
<apply id="Car_calculation">
<eq/>
<ci> Car </ci>
<apply>
<power/>
<apply>
<divide/>
<ci> Ca0 </ci>
<ci> Cac </ci>
</apply>
<ci> n_SK </ci>
</apply>
</apply>
<apply id="calcium_dependent_potassium_channel_m_gate_dm_dt">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> m </ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<minus/>
<ci> m </ci>
<ci> m_infinity </ci>
</apply>
</apply>
<ci> tau_m </ci>
</apply>
</apply>
</math>
</component>
<component name="buffered_calcium_diffusion">
<variable units="millimolar" public_interface="out" name="Bu"/>
<variable units="millimolar" public_interface="out" name="CaBu"/>
<variable units="per_millimolar_per_millisecond" public_interface="out" name="k1b" initial_value="100.0"/>
<variable units="per_millisecond" public_interface="out" name="k2b" initial_value="10.0"/>
<variable units="per_millisecond" public_interface="out" name="kfc"/>
<variable units="per_millisecond" public_interface="out" name="kbc"/>
<variable units="millimolar" name="Cai"/>
<variable units="millimolar" name="Cai2"/>
<variable units="micrometre2_per_millisecond" name="DCa" initial_value="0.22"/>
<variable units="micromolar_per_millisecond" name="FCai"/>
<variable units="millimolar" name="TBu" initial_value="4.0"/>
<variable units="micrometre" public_interface="in" name="delta_r"/>
<variable units="micrometre2" public_interface="in" name="Ai2"/>
<variable units="micrometre3" public_interface="in" name="vol_i"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="Cai_calculation">
<eq/>
<ci> Cai </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> CaBu </ci>
<ci> k2b </ci>
</apply>
<apply>
<times/>
<ci> Cai </ci>
<ci> Bu </ci>
<ci> k1b </ci>
</apply>
</apply>
</apply>
<apply id="Bu_calculation">
<eq/>
<ci> Bu </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> CaBu </ci>
<ci> k2b </ci>
</apply>
<apply>
<times/>
<ci> Cai </ci>
<ci> Bu </ci>
<ci> k1b </ci>
</apply>
</apply>
</apply>
<apply id="CaBu_calculation">
<eq/>
<ci> CaBu </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> Cai </ci>
<ci> Bu </ci>
<ci> k1b </ci>
</apply>
<apply>
<times/>
<ci> CaBu </ci>
<ci> k2b </ci>
</apply>
</apply>
</apply>
<apply id="FCai_calculation">
<eq/>
<ci> FCai </ci>
<apply>
<times/>
<apply>
<minus/>
<ci> Cai2 </ci>
<ci> Cai </ci>
</apply>
<ci> DCa </ci>
<apply>
<divide/>
<ci> Ai2 </ci>
<ci> delta_r </ci>
</apply>
</apply>
</apply>
<apply id="kfc_calculation">
<eq/>
<ci> kfc </ci>
<apply>
<divide/>
<apply>
<times/>
<ci> DCa </ci>
<ci> Ai2 </ci>
</apply>
<apply>
<times/>
<ci> delta_r </ci>
<ci> vol_i </ci>
</apply>
</apply>
</apply>
<apply id="kbc_calculation">
<eq/>
<ci> kbc </ci>
<apply>
<divide/>
<apply>
<times/>
<ci> DCa </ci>
<ci> Ai2 </ci>
</apply>
<apply>
<times/>
<ci> delta_r </ci>
<ci> vol_i </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="calcium_extrusion">
<variable units="microA_per_cm2" public_interface="out" name="i_ex"/>
<variable units="microA_per_cm2" name="Vmax" initial_value="3.0"/>
<variable units="nanomolar" name="Kex" initial_value="830.0"/>
<variable units="nanomolar" name="Ca_rest" initial_value="100.0"/>
<variable units="millimolar" public_interface="in" name="Ca0"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="i_ex_calculation">
<eq/>
<ci> i_ex </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> Vmax </ci>
<apply>
<divide/>
<ci> Ca0 </ci>
<apply>
<plus/>
<ci> Kex </ci>
<ci> Ca0 </ci>
</apply>
</apply>
</apply>
<apply>
<times/>
<ci> Vmax </ci>
<apply>
<divide/>
<ci> Ca_rest </ci>
<apply>
<plus/>
<ci> Kex </ci>
<ci> Ca_rest </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="calcium_triggered_exocytosis">
<variable units="millimolar_per_millisecond" name="SR"/>
<variable units="per_millisecond" name="k1f"/>
<variable units="per_millisecond" name="k1b"/>
<variable units="per_millisecond" name="k2"/>
<variable units="per_millisecond" name="a1" initial_value="9.0E-6"/>
<variable units="per_millisecond" name="a2" initial_value="5.5E-6"/>
<variable units="per_micromolar3_per_millisecond" name="a3" initial_value="2.3E-5"/>
<variable units="micromolar" name="b1" initial_value="1.2"/>
<variable units="dimensionless" name="B"/>
<variable units="dimensionless" name="A" initial_value="2000.0"/>
<variable units="dimensionless" name="C"/>
<variable units="millimolar" public_interface="in" name="Ca0"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="k1f_calculation">
<eq/>
<ci> k1f </ci>
<apply>
<times/>
<ci> a1 </ci>
<apply>
<divide/>
<ci> Ca0 </ci>
<apply>
<plus/>
<ci> b1 </ci>
<ci> Ca0 </ci>
</apply>
</apply>
</apply>
</apply>
<apply id="k1b_calculation">
<eq/>
<ci> k1b </ci>
<ci> a2 </ci>
</apply>
<apply id="k2_calculation">
<eq/>
<ci> k2 </ci>
<apply>
<times/>
<ci> a3 </ci>
<apply>
<power/>
<ci> Ca0 </ci>
<cn cellml:units="dimensionless"> 3.0 </cn>
</apply>
</apply>
</apply>
<apply id="B_calculation">
<eq/>
<ci> B </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> A </ci>
<ci> k1f </ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> B </ci>
<ci> k1b </ci>
</apply>
<apply>
<times/>
<ci> B </ci>
<ci> k2 </ci>
</apply>
</apply>
</apply>
</apply>
<apply id="C_calculation">
<eq/>
<ci> C </ci>
<apply>
<times/>
<ci> B </ci>
<ci> k2 </ci>
</apply>
</apply>
<apply id="SR_calculation">
<eq/>
<ci> SR </ci>
<apply>
<times/>
<ci> k2 </ci>
<ci> B </ci>
</apply>
</apply>
</math>
</component>
<component name="calcium_indicator">
<variable units="millimolar" public_interface="out" name="CaDy"/>
<variable units="millimolar" public_interface="out" name="Dy"/>
<variable units="per_millimolar_per_millisecond" public_interface="out" name="k1d" initial_value="500.0"/>
<variable units="per_millisecond" public_interface="out" name="k2d"/>
<variable units="millimolar" name="FDy"/>
<variable units="millimolar" name="Dyi2"/>
<variable units="millimolar" name="Cai"/>
<variable units="millimolar" name="FCaDy"/>
<variable units="micromolar" name="TDy" initial_value="5.0"/>
<variable units="micrometre2_per_millisecond" name="Ddy" initial_value="0.05"/>
<variable units="nanomolar" name="Dkd" initial_value="240.0"/>
<variable units="dimensionless" name="F0" initial_value="0.36"/>
<variable units="per_millisecond" name="kfd"/>
<variable units="per_millisecond" name="kbd"/>
<variable units="micrometre" public_interface="in" name="delta_r"/>
<variable units="micrometre2" public_interface="in" name="Ai2"/>
<variable units="micrometre3" public_interface="in" name="vol_i"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="Dy_calculation">
<eq/>
<ci> Dy </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> Dyi2 </ci>
<ci> kbd </ci>
</apply>
<apply>
<times/>
<ci> Dy </ci>
<ci> kfd </ci>
</apply>
</apply>
</apply>
<apply id="kfd_calculation">
<eq/>
<ci> kfd </ci>
<apply>
<divide/>
<apply>
<times/>
<ci> Ddy </ci>
<ci> Ai2 </ci>
</apply>
<apply>
<times/>
<ci> delta_r </ci>
<ci> vol_i </ci>
</apply>
</apply>
</apply>
<apply id="kbd_calculation">
<eq/>
<ci> kbd </ci>
<apply>
<divide/>
<apply>
<times/>
<ci> Ddy </ci>
<ci> Ai2 </ci>
</apply>
<apply>
<times/>
<ci> delta_r </ci>
<ci> vol_i </ci>
</apply>
</apply>
</apply>
<apply id="CaDy_calculation">
<eq/>
<ci> CaDy </ci>
<apply>
<minus/>
<apply>
<times/>
<ci> Dy </ci>
<ci> Cai </ci>
<ci> k1d </ci>
</apply>
<apply>
<times/>
<ci> CaDy </ci>
<ci> k2d </ci>
</apply>
</apply>
</apply>
<apply id="FDy_calculation">
<eq/>
<ci> FDy </ci>
<apply>
<plus/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> F0 </ci>
</apply>
<ci> FCaDy </ci>
</apply>
<ci> F0 </ci>
</apply>
</apply>
</math>
</component>
<component name="calcium_concentration">
<variable units="millimolar" public_interface="out" name="Ca0"/>
<variable units="micrometre2" name="A0"/>
<variable units="micrometre3" name="vol0"/>
<variable units="millimolar" name="Ca1"/>
<variable units="millisecond" public_interface="in" name="time"/>
<variable units="microA_per_cm2" public_interface="in" name="i_Ca"/>
<variable units="microA_per_cm2" public_interface="in" name="i_ex"/>
<variable units="millimolar" public_interface="in" name="CaBu"/>
<variable units="millimolar" public_interface="in" name="Bu"/>
<variable units="millimolar" public_interface="in" name="CaDy"/>
<variable units="millimolar" public_interface="in" name="Dy"/>
<variable units="coulomb_per_mole" public_interface="in" name="F"/>
<variable units="per_millimolar_per_millisecond" public_interface="in" name="k1d"/>
<variable units="per_millisecond" public_interface="in" name="k2d"/>
<variable units="per_millimolar_per_millisecond" public_interface="in" name="k1b"/>
<variable units="per_millisecond" public_interface="in" name="k2b"/>
<variable units="per_millisecond" public_interface="in" name="kfc"/>
<variable units="per_millisecond" public_interface="in" name="kbc"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="Ca0_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> Ca0 </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci> kbc </ci>
<ci> Ca1 </ci>
</apply>
<apply>
<times/>
<ci> k2b </ci>
<ci> CaBu </ci>
</apply>
<apply>
<times/>
<ci> k2d </ci>
<ci> CaDy </ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<divide/>
<apply>
<times/>
<apply>
<plus/>
<ci> i_Ca </ci>
<ci> i_ex </ci>
</apply>
<ci> A0 </ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless"> 2.0 </cn>
<ci> F </ci>
<ci> vol0 </ci>
</apply>
</apply>
<apply>
<times/>
<ci> kfc </ci>
<ci> Ca0 </ci>
</apply>
<apply>
<times/>
<ci> k1b </ci>
<ci> Bu </ci>
<ci> Ca0 </ci>
</apply>
<apply>
<times/>
<ci> k1d </ci>
<ci> Dy </ci>
<ci> Ca0 </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="model_parameters">
<variable units="joule_per_mole_kelvin" public_interface="out" name="R" initial_value="8.3144"/>
<variable units="kelvin" public_interface="out" name="T" initial_value="310.15"/>
<variable units="coulomb_per_mole" public_interface="out" name="F" initial_value="96485"/>
<variable units="micrometre" public_interface="out" name="delta_r"/>
<variable units="micrometre2" public_interface="out" name="Ai2"/>
<variable units="micrometre3" public_interface="out" name="vol_i"/>
<variable units="millivolt" public_interface="out" name="E_K" initial_value="-80.0"/>
<variable units="micrometre" name="diameter" initial_value="15.0"/>
<variable units="dimensionless" name="Nc" initial_value="6.0"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="delta_r_calculation">
<eq/>
<ci> delta_r </ci>
<apply>
<divide/>
<ci> diameter </ci>
<apply>
<times/>
<cn cellml:units="dimensionless"> 2.0 </cn>
<apply>
<minus/>
<ci> Nc </ci>
<cn cellml:units="dimensionless"> 1.0 </cn>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<group>
<relationship_ref relationship="containment"/>
<component_ref component="membrane">
<component_ref component="excitatory_synapse"/>
<component_ref component="calcium_channel">
<component_ref component="calcium_channel_m_gate"/>
<component_ref component="calcium_channel_h_gate"/>
</component_ref>
<component_ref component="sodium_channel">
<component_ref component="sodium_channel_m_gate"/>
<component_ref component="sodium_channel_h_gate"/>
</component_ref>
<component_ref component="potassium_channel">
<component_ref component="potassium_channel_n_gate"/>
</component_ref>
<component_ref component="calcium_dependent_potassium_channel">
<component_ref component="calcium_dependent_potassium_channel_m_gate"/>
</component_ref>
<component_ref component="buffered_calcium_diffusion"/>
<component_ref component="calcium_extrusion"/>
<component_ref component="calcium_triggered_exocytosis"/>
<component_ref component="calcium_indicator"/>
<component_ref component="calcium_concentration"/>
</component_ref>
</group>
<group>
<relationship_ref relationship="encapsulation"/>
<component_ref component="calcium_channel">
<component_ref component="calcium_channel_m_gate"/>
<component_ref component="calcium_channel_h_gate"/>
</component_ref>
<component_ref component="sodium_channel">
<component_ref component="sodium_channel_m_gate"/>
<component_ref component="sodium_channel_h_gate"/>
</component_ref>
<component_ref component="potassium_channel">
<component_ref component="potassium_channel_n_gate"/>
</component_ref>
<component_ref component="calcium_dependent_potassium_channel">
<component_ref component="calcium_dependent_potassium_channel_m_gate"/>
</component_ref>
</group>
<connection>
<map_components component_2="environment" component_1="membrane"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="sodium_channel"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="potassium_channel"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="calcium_channel"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="calcium_dependent_potassium_channel"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="calcium_concentration"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="excitatory_synapse" component_1="membrane"/>
<map_variables variable_2="i_sp" variable_1="i_sp"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="calcium_channel" component_1="membrane"/>
<map_variables variable_2="i_Ca" variable_1="i_Ca"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="sodium_channel" component_1="membrane"/>
<map_variables variable_2="i_Na" variable_1="i_Na"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="potassium_channel" component_1="membrane"/>
<map_variables variable_2="i_K" variable_1="i_K"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="calcium_dependent_potassium_channel" component_1="membrane"/>
<map_variables variable_2="i_SK" variable_1="i_SK"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="leak_channel" component_1="membrane"/>
<map_variables variable_2="i_l" variable_1="i_l"/>
<map_variables variable_2="V" variable_1="V"/>
</connection>
<connection>
<map_components component_2="calcium_extrusion" component_1="membrane"/>
<map_variables variable_2="i_ex" variable_1="i_ex"/>
</connection>
<connection>
<map_components component_2="calcium_channel" component_1="model_parameters"/>
<map_variables variable_2="F" variable_1="F"/>
<map_variables variable_2="R" variable_1="R"/>
<map_variables variable_2="T" variable_1="T"/>
</connection>
<connection>
<map_components component_2="buffered_calcium_diffusion" component_1="model_parameters"/>
<map_variables variable_2="delta_r" variable_1="delta_r"/>
<map_variables variable_2="Ai2" variable_1="Ai2"/>
<map_variables variable_2="vol_i" variable_1="vol_i"/>
</connection>
<connection>
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