Rendering of the source text

<?xml version='1.0' encoding='utf-8'?>
<!--  FILE :  fohlmeister_model_1997.xml

CREATED :  15th October 2003

LAST MODIFIED : 20th April 2005

AUTHOR :  Catherine Lloyd
          Bioengineering Institute
          The University of Auckland
          
MODEL STATUS :  This model conforms to the CellML 1.0 Specification released on
10th August 2001, and the CellML Metadata 1.0 Specification released on 16th
January, 2002.

DESCRIPTION :  This file contains a CellML description of Fohlmeister and Miller's 2003 computational model of the impulse encoding mechanics of ganglion cells in the tiger salamander retina.  

CHANGES
  20/04/2005 - PJV - Made MathML id's unique
  
--><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="fohlmeister_miller_1997_version01" name="fohlmeister_miller_1997_version01">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
  <articleinfo>
  <title>Modelling the Impulse Encoding Mechanisms of Ganglion Cells in the Tiger Salamander Retina</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>
The ganglion cells present in the vertebrate retina form the only pathway by which the retina and the brain communicate.  These output neurons translate the post-synaptic potentials into a pattern of impulses whose frequency is regulated by the synaptic current.  Voltage-clamp studies of retinal ganglion cells have suggested that there are at least five different ionic currents present, namely: <emphasis>I<subscript>Na</subscript>
          </emphasis>; <emphasis>I<subscript>Ca</subscript>
          </emphasis>; the non-activating, delayed rectifier <emphasis>I<subscript>K</subscript>
          </emphasis>; inactivating <emphasis>I<subscript>K,A</subscript>
          </emphasis>; and calcium-activated potassium currents <emphasis>I<subscript>K,Ca</subscript>
          </emphasis>.  In 1990, Fohlmeister <emphasis>et al.</emphasis> developed a mathematical model of ganglion cell impulse generation which was based on these five ionic currents.  The first four currents were modelled as being voltage-gated, while the fifth current, <emphasis>I<subscript>K,Ca</subscript>
          </emphasis>, is gated by [Ca<superscript>2+</superscript>]<subscript>i</subscript>.  The basic mathematical structure of the model is based on the Hodgkin-Huxley style of cellular modelling (see <ulink url="${HTML_EXMPL_HHSA_INTRO}">The Hodgkin-Huxley Squid Axon Model, 1952</ulink> for more details).  
</para>

<para>
This 1990 model appeared to provide a reasonably accurate representation of both the impulse waveform and repetitive firing behaviour of ganglion cells in the tiger salamander retina.  Model simulations suggested that <emphasis>I<subscript>K,Ca</subscript>
          </emphasis> might play an important role in stabilising the cell (i.e. preventing spontaneous firing), and also in regulating the interspike period.  To improve their understanding of this mechanism, in 1997, Fohlmeister and Miller combined new whole-cell experimental data together with pharmacological information and computer modelling to provide an integrated view of the experimental results, analysis, and simulation (see <xref linkend="fig_cell_diagram"/> below for a schematic diagram of their model).  
</para>

<para>
Model simulations suggested that <emphasis>I<subscript>Ca</subscript>
          </emphasis> and <emphasis>I<subscript>K,Ca</subscript>
          </emphasis> do play an important role in controlling impulse frequency.  But although this single compartment model was regarded as being qualitatively accurate in simulating impulse frequency behaviour and its underlying mechanisms, model limitations arose due to a lack of morphological data.  This issue was addressed in a detailed, multicompartmental model of the ganglion cell, which was published in a companion paper.
</para>

<para>
The model has been described here in CellML (the raw CellML description of the Fohlmeister and Miller 1997 model can be downloaded in various formats as described in <xref linkend="sec_download_this_model"/>).     
</para>

<para>
The complete original paper reference is cited below:
</para>

<para>
<ulink url="http://jn.physiology.org/cgi/content/abstract/78/4/1935">Impulse Encoding Mechanisms of Ganglion Cells in the Tiger Salamander Retina</ulink>, J. F. Fohlmeister and R. F. Miller, 1997, <ulink url="http://jn.physiology.org/">
            <emphasis>Journal of Neurophysiology</emphasis>
          </ulink>, 78, 1935-1947.  (<ulink url="http://jn.physiology.org/cgi/content/full/78/4/1935">Full text (HTML)</ulink> and <ulink url="http://jn.physiology.org/cgi/reprint/78/4/1935.pdf">PDF</ulink> versions of the article are available on the <emphasis>Journal of Neurophysiology</emphasis> website.)  <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;list_uids=9325362&amp;dopt=Abstract">PubMed ID: 9325362</ulink>
</para>

<informalfigure float="0" id="fig_cell_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>cell diagram</title>
    </objectinfo>
    <imagedata fileref="cell_diagram.gif"/>
  </imageobject>
</mediaobject>
<caption>A schematic illustration showing: A) a ganglion cell with its axon projecting upwards and its numerous dendrites projecting out from the soma; and B) the ionic currents across the plasma membrane of the cell.</caption>
</informalfigure>

</sect1>
</article>
</documentation>
  
  
  
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  <units name="millisecond">
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    <variable units="microA_per_cm2" public_interface="in" name="i_K"/>
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    <variable units="microA_per_cm2" public_interface="in" name="i_K_Ca"/>
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    </math>
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    <variable units="per_millisecond" name="beta_h"/>

    <variable units="millivolt" public_interface="in" name="V"/>
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    </math>
  </component> 
  
  <component name="calcium_channel">
    <variable units="microA_per_cm2" public_interface="out" name="i_Ca"/>
    
    <variable units="millivolt" name="E_Ca"/>
    <variable units="milliS_per_cm2" name="g_Ca" initial_value="2.2"/>
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  <component name="A_type_potassium_channel_h_gate">
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    <variable units="per_millisecond" name="alpha_h"/>
    <variable units="per_millisecond" name="beta_h"/>

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    <variable units="millisecond" public_interface="in" name="time"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
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      <apply id="A_type_potassium_channel_h_gate_beta_h_calculation">
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      <apply id="A_type_potassium_channel_h_gate_dh_dt">
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          <apply>
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            <ci> beta_h </ci>
            <ci> h </ci>
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        </apply>
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    </math>
  </component>  
  
  <component name="calcium_activated_potassium_channel">
    <variable units="microA_per_cm2" public_interface="out" name="i_K_Ca"/>
    
    <variable units="milliS_per_cm2" name="g_K_Ca" initial_value="0.05"/>
    <variable units="milliS_per_cm2" name="g_K_Ca_gate"/>
    
    <variable units="millivolt" public_interface="in" name="E_K"/>
    <variable units="millisecond" public_interface="in" name="time"/>
    <variable units="millivolt" public_interface="in" name="V"/>
    <variable units="millimolar" public_interface="in" name="Ca_i"/>
    <variable units="millimolar" public_interface="in" name="Ca_diss"/>
   
    <math xmlns="http://www.w3.org/1998/Math/MathML">
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            <minus/>
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            <ci> E_K </ci>
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      <apply id="g_K_Ca_gate_calculation">
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                  <ci> Ca_diss </ci>
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                <cn cellml:units="dimensionless"> 2.0 </cn>
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      </apply>
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  </component> 
  
  <component name="leakage_channel">
    <variable units="microA_per_cm2" public_interface="out" name="i_L"/>
    
    <variable units="milliS_per_cm2" name="g_L" initial_value="0.05"/>
    <variable units="millivolt" name="E_L" initial_value="-60.0"/>
    
    <variable units="millisecond" public_interface="in" name="time"/>
    <variable units="millivolt" public_interface="in" name="V"/>
   
    <math xmlns="http://www.w3.org/1998/Math/MathML">
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            <ci> E_L </ci>
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  <component name="parameters">
    <variable units="molar" public_interface="out" name="Ca_i" initial_value="1.0E-7"/>
    <variable units="millimolar" public_interface="out" name="Ca_e"/>
    <variable units="molar" public_interface="out" name="Ca_diss" initial_value="1.0E-6"/>
    <variable units="millivolt" public_interface="out" name="E_K" initial_value="-75.0"/>
    <variable units="coulomb_per_mole" public_interface="out" name="F" initial_value="96487.0"/>
    
    <variable units="millimolar" name="Ca_res" initial_value="1.0E-7"/>
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    <variable units="millisecond" public_interface="in" name="time"/>
    <variable units="microA_per_cm2" public_interface="in" name="i_Ca"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
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              <ci> Ca_res </ci>
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  <group>
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  <group>
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    <component_ref component="A_type_potassium_channel">
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  <connection>
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  <connection>
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  <connection>
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  <connection>
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  <connection>
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  <connection>
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  <connection>
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  <connection>
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  <connection>
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  <connection>
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  <connection>
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  <connection>
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  <connection>
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  <connection>
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  <connection>
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    <map_variables variable_2="m" variable_1="m"/>
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  <connection>
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    <map_variables variable_2="time" variable_1="time"/>
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  <connection>
    <map_components component_2="calcium_channel_c_gate" component_1="calcium_channel"/>
    <map_variables variable_2="c" variable_1="c"/>
    <map_variables variable_2="time" variable_1="time"/>
    <map_variables variable_2="V" variable_1="V"/>
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  <connection>
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    <map_variables variable_2="n" variable_1="n"/>
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  <connection>
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            Impulse Encoding Mechanisms of Ganglion Cells in the Tiger 
            Salamander Retina
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    <bqs:volume>78</bqs:volume>
    <bqs:first_page>1935</bqs:first_page>
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        The University of Auckland, Bioengineering Institute
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        Fohlmeister and Miller's 2003 computational model of the impulse 
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    <rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
    <vCard:N rdf:resource="rdf:#ba499a21-7a58-45cb-ae6c-695ed35bc46e"/>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#1bc21188-22c7-4a44-b6ec-1b77b90fd67e">
    <vCard:FN>Catherine Lloyd</vCard:FN>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#db74bc4a-fc08-4285-9aca-3c3eb95b2fe2">
    <bqs:subject_type>keyword</bqs:subject_type>
    <rdf:value rdf:resource="rdf:#1a65f735-c994-4fb0-9bc4-dbdb1494fe78"/>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#1328a7aa-c5cb-45c2-9338-ab1a86e44bee">
    <vCard:Given>J</vCard:Given>
    <vCard:Family>Fohlmeister</vCard:Family>
    <vCard:Other>F</vCard:Other>
  </rdf:Description>
</rdf:RDF>
</model>