<?xml version='1.0' encoding='utf-8'?>
<model
name="butera_single_cell_1999"
cmeta:id="butera_single_cell_1999"
xmlns="http://www.cellml.org/cellml/1.1#"
xmlns:cellml="http://www.cellml.org/cellml/1.1#"
xmlns:cmeta="http://www.cellml.org/metadata/1.0#"
xmlns:xlink="http://www.w3.org/1999/xlink"
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:dcterms="http://purl.org/dc/terms/"
xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" >
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Models of respiratory rhythm generation in the Pre-Botzinger complex. II. Populations of coupled pacemaker neurons</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 represents a single neuron in a network of cells. This cell model is based on "model 1" published in a preceding paper (Butera et al. 1999) which is also described in CellML as a stand alone CellML 1.0 model. To model inter-cellular coupling a synaptic input current I<subscript>syn_e</subscript> has been added to the model.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="butera_1999.png"/>
</imageobject>
</mediaobject>
<caption>The single cell neuron model is based on a single-compartment Hodgkin-Huxley type formalism. It is composed of five ionic currents across the plasma membrane: a fast sodium current, I<subscript>Na</subscript>; a delayed rectifier potassium current, I<subscript>K</subscript>; a persistent sodium current, I<subscript>NaP</subscript>; a passive leakage current, I<subscript>L</subscript>; and a tonic current, I<subscript>tonic_e</subscript> In addition for the multicellular model a synaptic current (I<subscript>syn_e</subscript>) has been added to connect the cells in the network.</caption>
</informalfigure>
<para>
The original paper reference is cited below:
</para>
<para>
Models of respiratory rhythm generation in the Pre-Botzinger complex. II. Populations Of coupled pacemaker neurons, Butera RJ Jr, Rinzel J, Smith JC, 1999, <emphasis>Journal of Neurophysiology</emphasis>, 82, 398-415. <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/10400967">PubMed ID: 10400967</ulink>
</para>
</sect1>
</article>
</documentation>
<cmeta:comment rdf:parseType="Resource">
<rdf:value>
This CellML model describes the single cell (neuron) of the Butera et al. 1999 model. This model is imported by the multicellular model 10 times.
</rdf:value>
<dc:creator rdf:parseType="Resource">
<vCard:FN>Catherine Lloyd</vCard:FN>
</dc:creator>
</cmeta:comment>
<units name="millisecond">
<unit units="second" prefix="milli"/>
</units>
<units name="millivolt">
<unit units="volt" prefix="milli"/>
</units>
<units name="picoA">
<unit units="ampere" prefix="nano"/>
</units>
<units name="nanoS">
<unit units="siemens" prefix="nano"/>
</units>
<units name="picoF">
<unit units="farad" prefix="pico"/>
</units>
<cmeta:comment rdf:parseType="Resource">
<rdf:value>
In order to facilitate the import of this single cell model by the multicellular model the current model is encapsulated in a top component called "single_neuron_model".
</rdf:value>
<dc:creator rdf:parseType="Resource">
<vCard:FN>Catherine Lloyd</vCard:FN>
</dc:creator>
</cmeta:comment>
<component name="single_neuron_model" cmeta:id="single_neuron_model">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/0P/PP-rdf-syntax-ns#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/">
<rdf:Description rdf:about="#single_neuron_model">
<dc:title>single_neuron_model</dc:title>
<dcterms:alternative>top component which encapsulates the single neuron cell model</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable name="s" public_interface="out" private_interface="in" units="dimensionless" />
<variable name="sum_g_syn_e_s" public_interface="in" private_interface="out" units="nanoS" />
</component>
<connection>
<map_components component_1="single_neuron_model" component_2="synaptic_input" />
<map_variables variable_1="sum_g_syn_e_s" variable_2="sum_g_syn_e_s" />
<map_variables variable_1="s" variable_2="s" />
</connection>
<component name="environment">
<variable units="millisecond" public_interface="out" name="time"/>
</component>
<component name="membrane">
<variable units="millivolt" public_interface="out" name="V" initial_value="-50.0"/>
<variable units="picoF" name="C" initial_value="21.0"/>
<variable units="picoA" name="i_app" initial_value="0.0"/>
<variable units="millisecond" public_interface="in" name="time"/>
<variable units="picoA" public_interface="in" name="i_NaP"/>
<variable units="picoA" public_interface="in" name="i_Na"/>
<variable units="picoA" public_interface="in" name="i_K"/>
<variable units="picoA" public_interface="in" name="i_L"/>
<variable units="picoA" public_interface="in" name="i_tonic_e"/>
<variable units="picoA" public_interface="in" name="i_syn_e"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="membrane_voltage_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> V </ci>
</apply>
<apply>
<divide/>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<plus/>
<ci> i_NaP </ci>
<ci> i_Na </ci>
<ci> i_K </ci>
<ci> i_L </ci>
<ci> i_tonic_e </ci>
<ci> i_syn_e </ci>
</apply>
</apply>
<ci> i_app </ci>
</apply>
<ci> C </ci>
</apply>
</apply>
</math>
</component>
<component name="fast_sodium_current">
<variable units="picoA" public_interface="out" name="i_Na"/>
<variable units="millivolt" public_interface="out" name="E_Na" initial_value="50.0"/>
<variable units="nanoS" name="g_Na" initial_value="28.0"/>
<variable units="millisecond" public_interface="in" private_interface="out" name="time"/>
<variable units="millivolt" public_interface="in" private_interface="out" name="V"/>
<variable units="dimensionless" private_interface="in" name="m_infinity"/>
<variable units="dimensionless" private_interface="in" name="n"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="i_Na_calculation">
<eq/>
<ci> i_Na </ci>
<apply>
<times/>
<ci> g_Na </ci>
<apply>
<power/>
<ci> m_infinity </ci>
<cn cellml:units="dimensionless"> 3.0 </cn>
</apply>
<apply>
<minus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> n </ci>
</apply>
<apply>
<minus/>
<ci> V </ci>
<ci> E_Na </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="fast_sodium_current_m_gate">
<variable units="dimensionless" public_interface="out" name="m_infinity"/>
<variable units="millivolt" name="theta_m" initial_value="-34.0"/>
<variable units="millivolt" name="sigma_m" initial_value="-5.0"/>
<variable units="millivolt" public_interface="in" name="V"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="fast_sodium_current_m_gate_m_infinity_calculation">
<eq/>
<ci> m_infinity </ci>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci> V </ci>
<ci> theta_m </ci>
</apply>
<ci> sigma_m </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="fast_sodium_current_n_gate">
<variable units="dimensionless" public_interface="out" name="n" initial_value="0.01"/>
<variable units="dimensionless" name="n_infinity"/>
<variable units="millisecond" name="tau_n"/>
<variable units="millisecond" name="tau_n_max" initial_value="10.0"/>
<variable units="millivolt" name="theta_n" initial_value="-29.0"/>
<variable units="millivolt" name="sigma_n" initial_value="-4.0"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="millisecond" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="fast_sodium_current_n_gate_n_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> n </ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci> n_infinity </ci>
<ci> n </ci>
</apply>
<ci> tau_n </ci>
</apply>
</apply>
<apply id="fast_sodium_current_n_gate_n_infinity_calculation">
<eq/>
<ci> n_infinity </ci>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci> V </ci>
<ci> theta_n </ci>
</apply>
<ci> sigma_n </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="fast_sodium_current_n_gate_tau_n_calculation">
<eq/>
<ci> tau_n </ci>
<apply>
<divide/>
<ci> tau_n_max </ci>
<apply>
<cosh/>
<apply>
<divide/>
<apply>
<minus/>
<ci> V </ci>
<ci> theta_n </ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless"> 2.0 </cn>
<ci> sigma_n </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="potassium_current">
<variable units="picoA" public_interface="out" name="i_K"/>
<variable units="nanoS" name="g_K" initial_value="11.2"/>
<variable units="millivolt" name="E_K" initial_value="-85.0"/>
<variable units="millisecond" public_interface="in" private_interface="out" name="time"/>
<variable units="millivolt" public_interface="in" private_interface="out" name="V"/>
<variable units="dimensionless" private_interface="in" name="n"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="i_K_calculation">
<eq/>
<ci> i_K </ci>
<apply>
<times/>
<ci> g_K </ci>
<apply>
<power/>
<ci> n </ci>
<cn cellml:units="dimensionless"> 4.0 </cn>
</apply>
<apply>
<minus/>
<ci> V </ci>
<ci> E_K </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="potassium_current_n_gate">
<variable units="dimensionless" public_interface="out" name="n" initial_value="0.01"/>
<variable units="dimensionless" name="n_infinity"/>
<variable units="millisecond" name="tau_n"/>
<variable units="millisecond" name="tau_n_max" initial_value="10.0"/>
<variable units="millivolt" name="theta_n" initial_value="-29.0"/>
<variable units="millivolt" name="sigma_n" initial_value="-4.0"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="millisecond" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="potassium_current_n_gate_n_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> n </ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci> n_infinity </ci>
<ci> n </ci>
</apply>
<ci> tau_n </ci>
</apply>
</apply>
<apply id="potassium_current_n_gate_n_infinity_calculation">
<eq/>
<ci> n_infinity </ci>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci> V </ci>
<ci> theta_n </ci>
</apply>
<ci> sigma_n </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="potassium_current_n_gate_tau_n_calculation">
<eq/>
<ci> tau_n </ci>
<apply>
<divide/>
<ci> tau_n_max </ci>
<apply>
<cosh/>
<apply>
<divide/>
<apply>
<minus/>
<ci> V </ci>
<ci> theta_n </ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless"> 2.0 </cn>
<ci> sigma_n </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="persistent_sodium_current">
<variable units="picoA" public_interface="out" name="i_NaP"/>
<variable units="nanoS" name="g_NaP" initial_value="2.8"/>
<variable units="millisecond" public_interface="in" private_interface="out" name="time"/>
<variable units="millivolt" public_interface="in" private_interface="out" name="V"/>
<variable units="millivolt" public_interface="in" name="E_Na"/>
<variable units="dimensionless" private_interface="in" name="m_infinity"/>
<variable units="dimensionless" private_interface="in" name="h"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="i_NaP_calculation">
<eq/>
<ci> i_NaP </ci>
<apply>
<times/>
<ci> g_NaP </ci>
<ci> m_infinity </ci>
<ci> h </ci>
<apply>
<minus/>
<ci> V </ci>
<ci> E_Na </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="persistent_sodium_current_m_gate">
<variable units="dimensionless" public_interface="out" name="m_infinity"/>
<variable units="millivolt" name="theta_m" initial_value="-40.0"/>
<variable units="millivolt" name="sigma_m" initial_value="-6.0"/>
<variable units="millivolt" public_interface="in" name="V"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="persistent_sodium_current_m_gate_m_infinity_calculation">
<eq/>
<ci> m_infinity </ci>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci> V </ci>
<ci> theta_m </ci>
</apply>
<ci> sigma_m </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="persistent_sodium_current_h_gate">
<variable units="dimensionless" public_interface="out" name="h" initial_value="0.46"/>
<variable units="dimensionless" name="h_infinity"/>
<variable units="millisecond" name="tau_h"/>
<variable units="millisecond" name="tau_h_max" initial_value="10000.0"/>
<variable units="millivolt" name="theta_h" initial_value="-48.0"/>
<variable units="millivolt" name="sigma_h" initial_value="6.0"/>
<variable units="millivolt" public_interface="in" name="V"/>
<variable units="millisecond" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="h_diff_eq">
<eq/>
<apply>
<diff/>
<bvar>
<ci> time </ci>
</bvar>
<ci> h </ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci> h_infinity </ci>
<ci> h </ci>
</apply>
<ci> tau_h </ci>
</apply>
</apply>
<apply id="h_infinity_calculation">
<eq/>
<ci> h_infinity </ci>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci> V </ci>
<ci> theta_h </ci>
</apply>
<ci> sigma_h </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="tau_h_calculation">
<eq/>
<ci> tau_h </ci>
<apply>
<divide/>
<ci> tau_h_max </ci>
<apply>
<cosh/>
<apply>
<divide/>
<apply>
<minus/>
<ci> V </ci>
<ci> theta_h </ci>
</apply>
<apply>
<times/>
<cn cellml:units="dimensionless"> 2.0 </cn>
<ci> sigma_h </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="leakage_current">
<variable units="picoA" public_interface="out" name="i_L"/>
<variable units="nanoS" name="g_L" initial_value="2.8"/>
<variable units="millivolt" name="E_L" initial_value="-57.5"/>
<variable units="millivolt" public_interface="in" name="V"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="i_L_calculation">
<eq/>
<ci> i_L </ci>
<apply>
<times/>
<ci> g_L </ci>
<apply>
<minus/>
<ci> V </ci>
<ci> E_L </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="tonic_current">
<variable units="picoA" public_interface="out" name="i_tonic_e"/>
<variable units="millivolt" name="E_syn_e" initial_value="0.0"/>
<variable units="nanoS" name="g_tonic_e" initial_value="0.0"/>
<variable units="millivolt" public_interface="in" name="V"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="i_tonic_e_calculation">
<eq/>
<ci> i_tonic_e </ci>
<apply>
<times/>
<ci> g_tonic_e </ci>
<apply>
<minus/>
<ci> V </ci>
<ci> E_syn_e </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="synaptic_input">
<variable units="picoA" public_interface="out" name="i_syn_e"/>
<variable units="dimensionless" private_interface="out" name="s"/>
<variable units="dimensionless" name="s_infinity"/>
<variable units="dimensionless" name="kr" initial_value="1.0"/>
<variable units="millisecond" name="tau_s" initial_value="5.0"/>
<variable units="millivolt" name="sigma_s" initial_value="-5.0"/>
<variable units="millivolt" name="theta_s" initial_value="-10.0"/>
<variable units="millivolt" public_interface="in" name="E_syn_e"/>
<variable units="nanoS" public_interface="in" name="sum_g_syn_e_s"/>
<variable units="millivolt" public_interface="in" name="V"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="i_syn_e_calculation">
<eq/>
<ci> i_syn_e </ci>
<apply>
<times/>
<ci> sum_g_syn_e_s </ci>
<apply>
<minus/>
<ci> V </ci>
<ci> E_syn_e </ci>
</apply>
</apply>
</apply>
<apply id="s_infinity_calculation">
<eq/>
<ci> s_infinity </ci>
<apply>
<divide/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<plus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<divide/>
<apply>
<minus/>
<ci> V </ci>
<ci> theta_s </ci>
</apply>
<ci> sigma_s </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="s_calculation">
<eq/>
<ci> s </ci>
<apply>
<divide/>
<apply>
<minus/>
<apply>
<times/>
<apply>
<minus/>
<cn cellml:units="dimensionless"> 1.0 </cn>
<ci> s </ci>
</apply>
<ci> s_infinity </ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci> kr </ci>
<ci> s </ci>
</apply>
</apply>
</apply>
<ci> tau_s </ci>
</apply>
</apply>
</math>
</component>
<group>
<relationship_ref relationship="encapsulation"/>
<component_ref component="single_neuron_model">
<component_ref component="environment"/>
<component_ref component="membrane"/>
<component_ref component="fast_sodium_current">
<component_ref component="fast_sodium_current_m_gate"/>
<component_ref component="fast_sodium_current_n_gate"/>
</component_ref>
<component_ref component="potassium_current">
<component_ref component="potassium_current_n_gate"/>
</component_ref>
<component_ref component="persistent_sodium_current">
<component_ref component="persistent_sodium_current_m_gate"/>
<component_ref component="persistent_sodium_current_h_gate"/>
</component_ref>
<component_ref component="leakage_current"/>
<component_ref component="tonic_current"/>
<component_ref component="synaptic_input"/>
</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="fast_sodium_current"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="potassium_current"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="persistent_sodium_current"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="membrane" component_1="fast_sodium_current"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_Na" variable_1="i_Na"/>
</connection>
<connection>
<map_components component_2="membrane" component_1="potassium_current"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_K" variable_1="i_K"/>
</connection>
<connection>
<map_components component_2="membrane" component_1="persistent_sodium_current"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_NaP" variable_1="i_NaP"/>
</connection>
<connection>
<map_components component_2="membrane" component_1="leakage_current"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_L" variable_1="i_L"/>
</connection>
<connection>
<map_components component_2="membrane" component_1="tonic_current"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_tonic_e" variable_1="i_tonic_e"/>
</connection>
<connection>
<map_components component_2="membrane" component_1="synaptic_input"/>
<map_variables variable_2="V" variable_1="V"/>
<map_variables variable_2="i_syn_e" variable_1="i_syn_e"/>
</connection>
<connection>
<map_components component_2="tonic_current" component_1="synaptic_input"/>
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Models of Respiratory Rhythm Generation in the Pre-Botzinger Complex. II. Populations of Coupled Pacemaker Neurons
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