Rendering of the source text

<?xml version='1.0' encoding='utf-8'?>
<!--  FILE :  bertram_model_2004.xml

CREATED :  2nd September 2004

LAST MODIFIED : 2nd September 2004

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 16/01/2002 CellML Metadata 1.0 Specification.

DESCRIPTION :  This file contains a CellML description of Bertram and Sherman's
calcium-based phantom bursting model for pancreatic islets. 

CHANGES:  
   
--><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#" name="bertram_sherman_2004_version01" cmeta:id="bertram_sherman_2004_version01">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
  <articleinfo>
  <title>A Calcium-based Phantom Bursting Model for Pancreatic Islets</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 model is has consistent units and has been verified as valid CellML by ValidateCellML. It is currently unsuitably constrained and can not be solved.
          </para>
  </section>
  <sect1 id="sec_structure">
<title>Model Structure</title>

<para>
Pancreatic beta-cells are located in clusters within the pancreas called the islets of Langerhans.  Beta-cells secrete the hormone insulin in response to elevated blood glucose levels, and in doing so, they play an essential role in glucose homeostasis.  When beta-cells fail to function properly, this can lead to pathologies such as type II diabetes.
</para> 

<para>
Insulin secretion is oscillatory, and it is in-phase with oscillations in the free cytosolic calcium concentration ([Ca<superscript>2+</superscript>]<subscript>i</subscript>), and theses Ca<superscript>2+</superscript> oscillations reflect a bursting pattern in the beta-cell electrical activity.  Electrical bursting consists of periodic active phases of cell firing (excitation) followed by silent phases of hyperpolarisation (rest).  These oscillations can be divided into three categories:
</para>
<itemizedlist>
  <listitem>
            <para>
              <emphasis>Fast bursting</emphasis>, which has a period between 2 and 5 seconds and which often occurs in single cells and in islets where acetylcholine is present;</para>
          </listitem>
  <listitem>
            <para>
              <emphasis>Medium bursting</emphasis>, which has a period of 10 to 60 seconds and which occurs in islets where there is a stimulatory glucose concentration; and</para>
          </listitem>
  <listitem>
            <para>
              <emphasis>Slow bursting</emphasis>, which has a period of 2 to 4 minutes and which occurs in single cells and in islets.</para>
          </listitem>
</itemizedlist>

<para>
The first mathematical models of beta-cells were developed to describe medium bursting, and the first models to address the variability in beta-cell oscillations were developed by Chay in 1995 and 1997 (see <ulink url="${HTML_EXMPL_CHAY_MODEL97}">Extracellular and Intracellular Calcium Effects on Pancreatic Beta Cells, Chay, 1997</ulink> for more details).  In these models the main mechanism for oscillations was variation in the Ca<superscript>2+</superscript> concentration in the ER, which directly or indirectly modulates one or more Ca<superscript>2+</superscript>-dependent channels.  In the Bertram and Sherman model described here the authors analyse in detail how the ER exerts its affects using a phantom bursting model (see <xref linkend="fig_cell_diagram"/> below). 
</para>

<para>
The phantom bursting model is a general paradigm for temporal plasticity in bursting in beta-cells in which bursting is driven by the interaction of two slow variables with disparate time constants (see <ulink url="${HTML_EXMPL_BERTRAM_MODEL}">The Phantom Burster Model for Pancreatic Beta-Cells, 2000</ulink> for more details).  There are three potential slow variables which could drive the phantom bursting <emphasis>in vivo</emphasis>:
</para>
<itemizedlist>
  <listitem>
            <para>cytosolic Ca<superscript>2+</superscript> concentration;</para>
          </listitem>
  <listitem>
            <para>ER Ca<superscript>2+</superscript> concentration;</para>
          </listitem>
  <listitem>
            <para>and the ADP to ATP ratio.</para>
          </listitem>
</itemizedlist>

<para>
The model has been described here in CellML (the raw CellML description of the Bertram and Sherman 2004 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://www.sciencedirect.com/science?_ob=ArticleURL&amp;_udi=B6WC7-4BS4GC2-1&amp;_user=140507&amp;_coverDate=09%2F30%2F2004&amp;_alid=197872630&amp;_rdoc=1&amp;_fmt=summary&amp;_orig=search&amp;_qd=1&amp;_cdi=6731&amp;_sort=d&amp;_docanchor=&amp;view=c&amp;_acct=C000011498&amp;_version=1&amp;_urlVersion=0&amp;_userid=140507&amp;md5=e1fdd19a27b1c7938c1d568e59a560e0">A Calcium-based Phantom Bursting Model for Pancreatic Islets</ulink>, Richard Bertram and Arthur Sherman, 2004, <ulink url="http://www.molbiolcell.org/">
            <emphasis>Bulletin of Mathematical Biology</emphasis>
          </ulink>, 66, 1313-1344.  (<ulink url="http://www.sciencedirect.com/science?_ob=ArticleURL&amp;_udi=B6WC7-4BS4GC2-1&amp;_coverDate=09%2F30%2F2004&amp;_alid=197872630&amp;_rdoc=1&amp;_fmt=&amp;_orig=search&amp;_qd=1&amp;_cdi=6731&amp;_sort=d&amp;view=c&amp;_acct=C000011498&amp;_version=1&amp;_urlVersion=0&amp;_userid=140507&amp;md5=b34962c344ab1a8911383073cd53016f">Full text (HTML)</ulink> and <ulink url="http://www.sciencedirect.com/science?_ob=MImg&amp;_imagekey=B6WC7-4BS4GC2-1-3Y&amp;_cdi=6731&amp;_orig=search&amp;_coverDate=09%2F30%2F2004&amp;_qd=1&amp;_sk=999339994&amp;view=c&amp;wchp=dGLbVzz-zSkWz&amp;_acct=C000011498&amp;_version=1&amp;_userid=140507&amp;md5=4f701b4338556df3136f0c4815596563&amp;ie=f.pdf">PDF</ulink> versions of the article are available to subscribers on the <emphasis>Bulletin of Mathematical Biology</emphasis> website.)  <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&amp;db=PubMed&amp;list_uids=15294427&amp;dopt=Abstract">PubMed ID: 15294427</ulink>
</para>

<informalfigure float="0" id="fig_cell_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>cell diagram</title>
    </objectinfo>
    <imagedata fileref="bertram_2004.png"/>
  </imageobject>
</mediaobject>
<caption>A schematic diagram of the ionic currents and fluxes across the ER and the cell surface membranes, which are described by the mathematical model.</caption>
</informalfigure>

</sect1>
</article>
</documentation>
  
  
  
  <units name="millisecond">
    <unit units="second" prefix="milli"/>
  </units>
  
  <units name="millivolt">
    <unit units="volt" prefix="milli"/>
  </units>
  
  <units name="micromolar">
    <unit units="mole" prefix="micro"/>
    <unit units="litre" exponent="-1"/>
  </units>
  
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  </units>
  
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  </units>
  
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  </units>
  
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  </component>
  
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      </apply>
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  <component name="calcium_current_m_gate">
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