Location: semantic-annotation @ 0d001436fb31 / eskandari_2005.cellml

Author:
Dewan Sarwar <dsar941@UoA.auckland.ac.nz>
Date:
2020-02-08 00:13:31+13:00
Desc:
updated a minor typo in the protocol4B sedml
Permanent Source URI:
https://models.cellml.org/workspace/267/rawfile/0d001436fb31391c678cc5d3d51e2f92a40e8f5b/eskandari_2005.cellml

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  <documentation xmlns="http://cellml.org/tmp-documentation">
    <article>
      <articleinfo>
        <title>Kinetics of the Reverse Mode of the Na+/Glucose Cotransporter</title>
        <author>
          <firstname>Jonna</firstname>
          <surname>Terkildsen</surname>
          <affiliation>
            <shortaffil>Auckland Bioengineering Institute, University of Auckland</shortaffil>
          </affiliation>
        </author>
      </articleinfo>
      <sect1 id="sec_status">
        <title>Model Status</title>
        <para>This CellML model is in the process of being curated, the units are consistent and the model runs in COR and PCEnv. This model does not yet recreate all the published results.</para>
      </sect1>
      <sect1 id="sec_structure">
        <title>Model Structure</title>
        <para>Abstract: This study investigates the reverse mode of the Na/glucose cotransporter (SGLT1). In giant excised inside-out membrane patches from Xenopus laevis oocytes expressing rabbit SGLT1, application of a-methyl-D-glucopyranoside (aMDG) to the cytoplasmic solution induced an outward current from cytosolic to external membrane surface. The outward current was Na- and sugar-dependent, and was blocked by phlorizin, a specific inhibitor of SGLT1. The current-voltage relationship saturated at positive membrane voltages (30-50 mV), and approached zero at -150 mV. The half-maximal concentration for aMDG-evoked outward current (K_0.5_aMDG) was 35 mM (at 0 mV). In comparison, K_0.5_aMDG for forward sugar transport was 0.15 mM (at 0 mV). K_0.5_Na was similar for forward and reverse transport (~ 35mM at 0 mV). Specificity of SGLT1 for reverse transport was: aMDG (1.0) &gt; D-galactose (0.84) &gt; 3-O-methyl-glucose (0.55) &gt; D-glucose (0.38), whereas for forward transport, specificity was: aMDG ~ D-glucose ~ D-galactose &gt; 3-O-methylglucose. Thus there is an asymmetry in sugar kinetics and specificity between forward and reverse modes. Computer simulations showed that a 6-state kinetic model for SGLT1 can account for Na/sugar cotransport and its voltage dependence in both the forward and reverse modes at saturating sodium concentrations. Our data indicate that under physiological conditions, the transporter is poised to accumulate sugar efficiently in the enterocyte.</para>
        <para>The original paper reference is cited below:</para>
        <para>
          Kinetics of the Reverse Mode of the Na+/Glucose Cotransporter, S.Eskandari, E.M. Wright and D.D.F. Loo, 2005,
          <emphasis>Journal of Membrane Biology</emphasis>
          , 204, 23-32.
          <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&amp;cmd=Retrieve&amp;dopt=AbstractPlus&amp;list_uids=16007500&amp;query_hl=1&amp;itool=pubmed_docsum">PubMed ID: 16007500</ulink>
        </para>
        <informalfigure float="0" id="fig_reaction_diagram">
          <mediaobject>
            <imageobject>
              <objectinfo>
                <title>model diagram</title>
              </objectinfo>
              <imagedata fileref="eskandari_2005.png" />
            </imageobject>
          </mediaobject>
          <caption>Schematic diagram of the Eskandari et al 2005 SGLT1 model. C' represents the external-facing carrier. C'' represents the internal-facing carrier.</caption>
        </informalfigure>
      </sect1>
    </article>
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        <eq />
        <ci>k_54</ci>
        <apply>
          <times />
          <ci>k0_54_temp</ci>
          <ci>glucose_i</ci>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>k_25</ci>
        <apply>
          <times />
          <ci>k0_25</ci>
          <apply>
            <exp />
            <apply>
              <divide />
              <apply>
                <times />
                <apply>
                  <minus />
                  <apply>
                    <plus />
                    <ci>z_c</ci>
                    <ci>n</ci>
                  </apply>
                </apply>
                <ci>delta</ci>
                <ci>mu</ci>
              </apply>
              <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
            </apply>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>k_52_temp</ci>
        <apply>
          <times />
          <ci>k0_52</ci>
          <apply>
            <exp />
            <apply>
              <divide />
              <apply>
                <times />
                <apply>
                  <plus />
                  <ci>z_c</ci>
                  <ci>n</ci>
                </apply>
                <ci>delta</ci>
                <ci>mu</ci>
              </apply>
              <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
            </apply>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>k_56</ci>
        <apply>
          <times />
          <ci>k0_56</ci>
          <apply>
            <exp />
            <apply>
              <divide />
              <apply>
                <times />
                <apply>
                  <minus />
                  <ci>n</ci>
                </apply>
                <ci>z_Na</ci>
                <ci>alpha_pp</ci>
                <ci>mu</ci>
              </apply>
              <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
            </apply>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>k_65</ci>
        <apply>
          <times />
          <ci>k0_65</ci>
          <apply>
            <power />
            <ci>Na_i</ci>
            <ci>n</ci>
          </apply>
          <apply>
            <exp />
            <apply>
              <divide />
              <apply>
                <times />
                <ci>n</ci>
                <ci>z_Na</ci>
                <ci>alpha_pp</ci>
                <ci>mu</ci>
              </apply>
              <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
            </apply>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>k_61</ci>
        <apply>
          <times />
          <ci>k0_61</ci>
          <apply>
            <exp />
            <apply>
              <divide />
              <apply>
                <times />
                <ci>z_c</ci>
                <ci>delta</ci>
                <ci>mu</ci>
              </apply>
              <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
            </apply>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>k_16</ci>
        <apply>
          <times />
          <ci>k0_16</ci>
          <apply>
            <exp />
            <apply>
              <divide />
              <apply>
                <times />
                <apply>
                  <minus />
                  <ci>z_c</ci>
                </apply>
                <ci>delta</ci>
                <ci>mu</ci>
              </apply>
              <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">2</cn>
            </apply>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>k_52</ci>
        <apply>
          <divide />
          <apply>
            <times />
            <ci>k0_12</ci>
            <ci>k_25</ci>
            <ci>k0_56</ci>
            <ci>k0_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k0_21</ci>
            <ci>k0_16</ci>
            <ci>k0_65</ci>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>k0_54_temp</ci>
        <apply>
          <divide />
          <apply>
            <times />
            <ci>k0_23</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_52</ci>
          </apply>
          <apply>
            <times />
            <ci>k_43</ci>
            <ci>k_32</ci>
            <ci>k_25</ci>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  <component name="kinetic_equations">
    <variable cmeta:id="kinetic_equations.k_12" name="k_12" public_interface="in" units="per_second" />
    <variable cmeta:id="kinetic_equations.k_21" name="k_21" public_interface="in" units="per_second" />
    <variable cmeta:id="kinetic_equations.k_23" name="k_23" public_interface="in" units="per_second" />
    <variable cmeta:id="kinetic_equations.k_32" name="k_32" public_interface="in" units="per_second" />
    <variable cmeta:id="kinetic_equations.k_34" name="k_34" public_interface="in" units="per_second" />
    <variable cmeta:id="kinetic_equations.k_43" name="k_43" public_interface="in" units="per_second" />
    <variable cmeta:id="kinetic_equations.k_45" name="k_45" public_interface="in" units="per_second" />
    <variable cmeta:id="kinetic_equations.k_54" name="k_54" public_interface="in" units="per_second" />
    <variable cmeta:id="kinetic_equations.k_25" name="k_25" public_interface="in" units="per_second" />
    <variable cmeta:id="kinetic_equations.k_52" name="k_52" public_interface="in" units="per_second" />
    <variable cmeta:id="kinetic_equations.k_56" name="k_56" public_interface="in" units="per_second" />
    <variable cmeta:id="kinetic_equations.k_65" name="k_65" public_interface="in" units="per_second" />
    <variable cmeta:id="kinetic_equations.k_61" name="k_61" public_interface="in" units="per_second" />
    <variable cmeta:id="kinetic_equations.k_16" name="k_16" public_interface="in" units="per_second" />
    <variable cmeta:id="kinetic_equations.C_1" initial_value="0" name="C_1" public_interface="out" units="umol" />
    <variable cmeta:id="kinetic_equations.C_2" initial_value="0" name="C_2" public_interface="out" units="umol" />
    <variable cmeta:id="kinetic_equations.C_3" initial_value="0" name="C_3" public_interface="out" units="umol" />
    <variable cmeta:id="kinetic_equations.C_4" initial_value="0" name="C_4" public_interface="out" units="umol" />
    <variable cmeta:id="kinetic_equations.C_5" initial_value="0" name="C_5" public_interface="out" units="umol" />
    <variable cmeta:id="kinetic_equations.C_6" name="C_6" public_interface="out" units="umol" />
    <variable cmeta:id="kinetic_equations.C_6_temp" initial_value="0" name="C_6_temp" public_interface="out" units="umol" />
    <variable cmeta:id="kinetic_equations.C_T" name="C_T" public_interface="in" units="umol" />
    <variable cmeta:id="kinetic_equations.time" name="time" public_interface="in" units="second" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <apply>
          <diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>C_1</ci>
        </apply>
        <apply>
          <minus />
          <apply>
            <plus />
            <apply>
              <times />
              <ci>k_21</ci>
              <ci>C_2</ci>
            </apply>
            <apply>
              <times />
              <ci>k_61</ci>
              <ci>C_6</ci>
            </apply>
          </apply>
          <apply>
            <times />
            <apply>
              <plus />
              <ci>k_12</ci>
              <ci>k_16</ci>
            </apply>
            <ci>C_1</ci>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <apply>
          <diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>C_2</ci>
        </apply>
        <apply>
          <minus />
          <apply>
            <plus />
            <apply>
              <times />
              <ci>k_12</ci>
              <ci>C_1</ci>
            </apply>
            <apply>
              <times />
              <ci>k_32</ci>
              <ci>C_3</ci>
            </apply>
            <apply>
              <times />
              <ci>k_52</ci>
              <ci>C_5</ci>
            </apply>
          </apply>
          <apply>
            <times />
            <apply>
              <plus />
              <ci>k_21</ci>
              <ci>k_23</ci>
              <ci>k_25</ci>
            </apply>
            <ci>C_2</ci>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <apply>
          <diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>C_3</ci>
        </apply>
        <apply>
          <minus />
          <apply>
            <plus />
            <apply>
              <times />
              <ci>k_23</ci>
              <ci>C_2</ci>
            </apply>
            <apply>
              <times />
              <ci>k_43</ci>
              <ci>C_4</ci>
            </apply>
          </apply>
          <apply>
            <times />
            <apply>
              <plus />
              <ci>k_32</ci>
              <ci>k_34</ci>
            </apply>
            <ci>C_3</ci>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <apply>
          <diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>C_4</ci>
        </apply>
        <apply>
          <minus />
          <apply>
            <plus />
            <apply>
              <times />
              <ci>k_34</ci>
              <ci>C_3</ci>
            </apply>
            <apply>
              <times />
              <ci>k_54</ci>
              <ci>C_5</ci>
            </apply>
          </apply>
          <apply>
            <times />
            <apply>
              <plus />
              <ci>k_45</ci>
              <ci>k_43</ci>
            </apply>
            <ci>C_4</ci>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <apply>
          <diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>C_5</ci>
        </apply>
        <apply>
          <minus />
          <apply>
            <plus />
            <apply>
              <times />
              <ci>k_45</ci>
              <ci>C_4</ci>
            </apply>
            <apply>
              <times />
              <ci>k_65</ci>
              <ci>C_6</ci>
            </apply>
            <apply>
              <times />
              <ci>k_25</ci>
              <ci>C_2</ci>
            </apply>
          </apply>
          <apply>
            <times />
            <apply>
              <plus />
              <ci>k_54</ci>
              <ci>k_52</ci>
              <ci>k_56</ci>
            </apply>
            <ci>C_5</ci>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <apply>
          <diff />
          <bvar>
            <ci>time</ci>
          </bvar>
          <ci>C_6_temp</ci>
        </apply>
        <apply>
          <minus />
          <apply>
            <plus />
            <apply>
              <times />
              <ci>k_16</ci>
              <ci>C_1</ci>
            </apply>
            <apply>
              <times />
              <ci>k_56</ci>
              <ci>C_5</ci>
            </apply>
          </apply>
          <apply>
            <times />
            <apply>
              <plus />
              <ci>k_61</ci>
              <ci>k_65</ci>
            </apply>
            <ci>C_6_temp</ci>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>C_6</ci>
        <apply>
          <minus />
          <ci>C_T</ci>
          <apply>
            <plus />
            <ci>C_1</ci>
            <ci>C_2</ci>
            <ci>C_3</ci>
            <ci>C_4</ci>
            <ci>C_5</ci>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  <component name="king_altman_states">
    <variable cmeta:id="king_altman_states.k_12" name="k_12" public_interface="in" units="per_second" />
    <variable cmeta:id="king_altman_states.k_21" name="k_21" public_interface="in" units="per_second" />
    <variable cmeta:id="king_altman_states.k_23" name="k_23" public_interface="in" units="per_second" />
    <variable cmeta:id="king_altman_states.k_32" name="k_32" public_interface="in" units="per_second" />
    <variable cmeta:id="king_altman_states.k_34" name="k_34" public_interface="in" units="per_second" />
    <variable cmeta:id="king_altman_states.k_43" name="k_43" public_interface="in" units="per_second" />
    <variable cmeta:id="king_altman_states.k_45" name="k_45" public_interface="in" units="per_second" />
    <variable cmeta:id="king_altman_states.k_54" name="k_54" public_interface="in" units="per_second" />
    <variable cmeta:id="king_altman_states.k_25" name="k_25" public_interface="in" units="per_second" />
    <variable cmeta:id="king_altman_states.k_52" name="k_52" public_interface="in" units="per_second" />
    <variable cmeta:id="king_altman_states.k_56" name="k_56" public_interface="in" units="per_second" />
    <variable cmeta:id="king_altman_states.k_65" name="k_65" public_interface="in" units="per_second" />
    <variable cmeta:id="king_altman_states.k_61" name="k_61" public_interface="in" units="per_second" />
    <variable cmeta:id="king_altman_states.k_16" name="k_16" public_interface="in" units="per_second" />
    <variable cmeta:id="king_altman_states.C1_sum" name="C1_sum" units="per_second5" />
    <variable cmeta:id="king_altman_states.C2_sum" name="C2_sum" units="per_second5" />
    <variable cmeta:id="king_altman_states.C3_sum" name="C3_sum" units="per_second5" />
    <variable cmeta:id="king_altman_states.C4_sum" name="C4_sum" units="per_second5" />
    <variable cmeta:id="king_altman_states.C5_sum" name="C5_sum" units="per_second5" />
    <variable cmeta:id="king_altman_states.C6_sum" name="C6_sum" units="per_second5" />
    <variable cmeta:id="king_altman_states.C_sum" name="C_sum" units="per_second5" />
    <variable cmeta:id="king_altman_states.C_T" name="C_T" public_interface="in" units="umol" />
    <variable cmeta:id="king_altman_states.C1" name="C1" public_interface="out" units="umol" />
    <variable cmeta:id="king_altman_states.C2" name="C2" public_interface="out" units="umol" />
    <variable cmeta:id="king_altman_states.C3" name="C3" public_interface="out" units="umol" />
    <variable cmeta:id="king_altman_states.C4" name="C4" public_interface="out" units="umol" />
    <variable cmeta:id="king_altman_states.C5" name="C5" public_interface="out" units="umol" />
    <variable cmeta:id="king_altman_states.C6" name="C6" public_interface="out" units="umol" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <ci>C1_sum</ci>
        <apply>
          <plus />
          <apply>
            <times />
            <ci>k_21</ci>
            <ci>k_32</ci>
            <ci>k_43</ci>
            <ci>k_54</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_21</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_52</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_21</ci>
            <ci>k_32</ci>
            <ci>k_45</ci>
            <ci>k_52</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_21</ci>
            <ci>k_32</ci>
            <ci>k_43</ci>
            <ci>k_52</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_25</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_56</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_23</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_56</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_21</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_56</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_25</ci>
            <ci>k_32</ci>
            <ci>k_45</ci>
            <ci>k_56</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_21</ci>
            <ci>k_32</ci>
            <ci>k_45</ci>
            <ci>k_56</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_25</ci>
            <ci>k_32</ci>
            <ci>k_43</ci>
            <ci>k_56</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_21</ci>
            <ci>k_32</ci>
            <ci>k_43</ci>
            <ci>k_56</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_21</ci>
            <ci>k_32</ci>
            <ci>k_43</ci>
            <ci>k_54</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_21</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_52</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_21</ci>
            <ci>k_32</ci>
            <ci>k_45</ci>
            <ci>k_52</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_21</ci>
            <ci>k_32</ci>
            <ci>k_43</ci>
            <ci>k_52</ci>
            <ci>k_61</ci>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>C2_sum</ci>
        <apply>
          <plus />
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_32</ci>
            <ci>k_43</ci>
            <ci>k_54</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_32</ci>
            <ci>k_43</ci>
            <ci>k_54</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_52</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_52</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_32</ci>
            <ci>k_45</ci>
            <ci>k_52</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_32</ci>
            <ci>k_45</ci>
            <ci>k_52</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_32</ci>
            <ci>k_43</ci>
            <ci>k_52</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_32</ci>
            <ci>k_43</ci>
            <ci>k_52</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_56</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_32</ci>
            <ci>k_45</ci>
            <ci>k_56</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_32</ci>
            <ci>k_43</ci>
            <ci>k_56</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_32</ci>
            <ci>k_43</ci>
            <ci>k_54</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_52</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_32</ci>
            <ci>k_45</ci>
            <ci>k_52</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_32</ci>
            <ci>k_43</ci>
            <ci>k_52</ci>
            <ci>k_61</ci>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>C3_sum</ci>
        <apply>
          <plus />
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_25</ci>
            <ci>k_43</ci>
            <ci>k_54</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_25</ci>
            <ci>k_43</ci>
            <ci>k_54</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_23</ci>
            <ci>k_43</ci>
            <ci>k_54</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_23</ci>
            <ci>k_43</ci>
            <ci>k_54</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_21</ci>
            <ci>k_43</ci>
            <ci>k_54</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_23</ci>
            <ci>k_45</ci>
            <ci>k_52</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_23</ci>
            <ci>k_45</ci>
            <ci>k_52</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_23</ci>
            <ci>k_43</ci>
            <ci>k_52</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_23</ci>
            <ci>k_43</ci>
            <ci>k_52</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_23</ci>
            <ci>k_45</ci>
            <ci>k_56</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_23</ci>
            <ci>k_43</ci>
            <ci>k_56</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_25</ci>
            <ci>k_43</ci>
            <ci>k_54</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_23</ci>
            <ci>k_43</ci>
            <ci>k_54</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_23</ci>
            <ci>k_45</ci>
            <ci>k_52</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_23</ci>
            <ci>k_43</ci>
            <ci>k_52</ci>
            <ci>k_61</ci>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>C4_sum</ci>
        <apply>
          <plus />
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_25</ci>
            <ci>k_34</ci>
            <ci>k_54</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_25</ci>
            <ci>k_34</ci>
            <ci>k_54</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_23</ci>
            <ci>k_34</ci>
            <ci>k_54</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_23</ci>
            <ci>k_34</ci>
            <ci>k_54</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_21</ci>
            <ci>k_34</ci>
            <ci>k_54</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_25</ci>
            <ci>k_32</ci>
            <ci>k_54</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_25</ci>
            <ci>k_32</ci>
            <ci>k_54</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_21</ci>
            <ci>k_32</ci>
            <ci>k_54</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_23</ci>
            <ci>k_34</ci>
            <ci>k_52</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_23</ci>
            <ci>k_34</ci>
            <ci>k_52</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_23</ci>
            <ci>k_34</ci>
            <ci>k_56</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_25</ci>
            <ci>k_34</ci>
            <ci>k_54</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_23</ci>
            <ci>k_34</ci>
            <ci>k_54</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_25</ci>
            <ci>k_32</ci>
            <ci>k_54</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_23</ci>
            <ci>k_34</ci>
            <ci>k_52</ci>
            <ci>k_61</ci>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>C5_sum</ci>
        <apply>
          <plus />
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_25</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_25</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_23</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_23</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_21</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_25</ci>
            <ci>k_32</ci>
            <ci>k_45</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_25</ci>
            <ci>k_32</ci>
            <ci>k_45</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_21</ci>
            <ci>k_32</ci>
            <ci>k_45</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_25</ci>
            <ci>k_32</ci>
            <ci>k_43</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_25</ci>
            <ci>k_32</ci>
            <ci>k_43</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_21</ci>
            <ci>k_32</ci>
            <ci>k_43</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_25</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_23</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_25</ci>
            <ci>k_32</ci>
            <ci>k_45</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_25</ci>
            <ci>k_32</ci>
            <ci>k_43</ci>
            <ci>k_61</ci>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>C6_sum</ci>
        <apply>
          <plus />
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_25</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_56</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_25</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_56</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_23</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_56</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_23</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_56</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_21</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_56</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_25</ci>
            <ci>k_32</ci>
            <ci>k_45</ci>
            <ci>k_56</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_25</ci>
            <ci>k_32</ci>
            <ci>k_45</ci>
            <ci>k_56</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_21</ci>
            <ci>k_32</ci>
            <ci>k_45</ci>
            <ci>k_56</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_25</ci>
            <ci>k_32</ci>
            <ci>k_43</ci>
            <ci>k_56</ci>
          </apply>
          <apply>
            <times />
            <ci>k_12</ci>
            <ci>k_25</ci>
            <ci>k_32</ci>
            <ci>k_43</ci>
            <ci>k_56</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_21</ci>
            <ci>k_32</ci>
            <ci>k_43</ci>
            <ci>k_56</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_21</ci>
            <ci>k_32</ci>
            <ci>k_43</ci>
            <ci>k_54</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_21</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_52</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_21</ci>
            <ci>k_32</ci>
            <ci>k_45</ci>
            <ci>k_52</ci>
          </apply>
          <apply>
            <times />
            <ci>k_16</ci>
            <ci>k_21</ci>
            <ci>k_32</ci>
            <ci>k_43</ci>
            <ci>k_52</ci>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>C_sum</ci>
        <apply>
          <plus />
          <ci>C1_sum</ci>
          <ci>C2_sum</ci>
          <ci>C3_sum</ci>
          <ci>C4_sum</ci>
          <ci>C5_sum</ci>
          <ci>C6_sum</ci>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>C1</ci>
        <apply>
          <divide />
          <apply>
            <times />
            <ci>C_T</ci>
            <ci>C1_sum</ci>
          </apply>
          <ci>C_sum</ci>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>C2</ci>
        <apply>
          <divide />
          <apply>
            <times />
            <ci>C_T</ci>
            <ci>C2_sum</ci>
          </apply>
          <ci>C_sum</ci>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>C3</ci>
        <apply>
          <divide />
          <apply>
            <times />
            <ci>C_T</ci>
            <ci>C3_sum</ci>
          </apply>
          <ci>C_sum</ci>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>C4</ci>
        <apply>
          <divide />
          <apply>
            <times />
            <ci>C_T</ci>
            <ci>C4_sum</ci>
          </apply>
          <ci>C_sum</ci>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>C5</ci>
        <apply>
          <divide />
          <apply>
            <times />
            <ci>C_T</ci>
            <ci>C5_sum</ci>
          </apply>
          <ci>C_sum</ci>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>C6</ci>
        <apply>
          <divide />
          <apply>
            <times />
            <ci>C_T</ci>
            <ci>C6_sum</ci>
          </apply>
          <ci>C_sum</ci>
        </apply>
      </apply>
    </math>
  </component>
  <component name="NBC_current">
    <variable cmeta:id="NBC_current.k_12" name="k_12" public_interface="in" units="per_second" />
    <variable cmeta:id="NBC_current.k_21" name="k_21" public_interface="in" units="per_second" />
    <variable cmeta:id="NBC_current.k_56" name="k_56" public_interface="in" units="per_second" />
    <variable cmeta:id="NBC_current.k_65" name="k_65" public_interface="in" units="per_second" />
    <variable cmeta:id="NBC_current.k_34" name="k_34" public_interface="in" units="per_second" />
    <variable cmeta:id="NBC_current.k_43" name="k_43" public_interface="in" units="per_second" />
    <variable cmeta:id="NBC_current.k_25" name="k_25" public_interface="in" units="per_second" />
    <variable cmeta:id="NBC_current.k_52" name="k_52" public_interface="in" units="per_second" />
    <variable cmeta:id="NBC_current.k_61" name="k_61" public_interface="in" units="per_second" />
    <variable cmeta:id="NBC_current.k_16" name="k_16" public_interface="in" units="per_second" />
    <variable cmeta:id="NBC_current.C_1" name="C_1" public_interface="in" units="umol" />
    <variable cmeta:id="NBC_current.C_2" name="C_2" public_interface="in" units="umol" />
    <variable cmeta:id="NBC_current.C_3" name="C_3" public_interface="in" units="umol" />
    <variable cmeta:id="NBC_current.C_4" name="C_4" public_interface="in" units="umol" />
    <variable cmeta:id="NBC_current.C_5" name="C_5" public_interface="in" units="umol" />
    <variable cmeta:id="NBC_current.C_6" name="C_6" public_interface="in" units="umol" />
    <variable cmeta:id="NBC_current.C1" name="C1" public_interface="in" units="umol" />
    <variable cmeta:id="NBC_current.C2" name="C2" public_interface="in" units="umol" />
    <variable cmeta:id="NBC_current.C3" name="C3" public_interface="in" units="umol" />
    <variable cmeta:id="NBC_current.C4" name="C4" public_interface="in" units="umol" />
    <variable cmeta:id="NBC_current.C5" name="C5" public_interface="in" units="umol" />
    <variable cmeta:id="NBC_current.C6" name="C6" public_interface="in" units="umol" />
    <variable cmeta:id="NBC_current.delta" name="delta" public_interface="in" units="dimensionless" />
    <variable cmeta:id="NBC_current.alpha_p" name="alpha_p" public_interface="in" units="dimensionless" />
    <variable cmeta:id="NBC_current.alpha_pp" name="alpha_pp" public_interface="in" units="dimensionless" />
    <variable cmeta:id="NBC_current.n" name="n" public_interface="in" units="dimensionless" />
    <variable cmeta:id="NBC_current.z_c" name="z_c" public_interface="in" units="dimensionless" />
    <variable cmeta:id="NBC_current.z_Na" name="z_Na" public_interface="in" units="dimensionless" />
    <variable cmeta:id="NBC_current.F" name="F" public_interface="in" units="C_per_mol" />
    <variable cmeta:id="NBC_current.I_NaGl_pSS" name="I_NaGl_pSS" public_interface="out" units="uA" />
    <variable cmeta:id="NBC_current.I_NaGl_SS" name="I_NaGl_SS" public_interface="out" units="uA" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <ci>I_NaGl_pSS</ci>
        <apply>
          <times />
          <apply>
            <minus />
            <ci>F</ci>
          </apply>
          <apply>
            <plus />
            <apply>
              <times />
              <ci>n</ci>
              <ci>z_Na</ci>
              <ci>alpha_p</ci>
              <apply>
                <minus />
                <apply>
                  <times />
                  <ci>k_12</ci>
                  <ci>C_1</ci>
                </apply>
                <apply>
                  <times />
                  <ci>k_21</ci>
                  <ci>C_2</ci>
                </apply>
              </apply>
            </apply>
            <apply>
              <times />
              <ci>z_c</ci>
              <ci>delta</ci>
              <apply>
                <minus />
                <apply>
                  <times />
                  <ci>k_16</ci>
                  <ci>C_1</ci>
                </apply>
                <apply>
                  <times />
                  <ci>k_61</ci>
                  <ci>C_6</ci>
                </apply>
              </apply>
            </apply>
            <apply>
              <times />
              <ci>n</ci>
              <ci>z_Na</ci>
              <ci>alpha_pp</ci>
              <apply>
                <minus />
                <apply>
                  <times />
                  <ci>k_56</ci>
                  <ci>C_5</ci>
                </apply>
                <apply>
                  <times />
                  <ci>k_65</ci>
                  <ci>C_6</ci>
                </apply>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>I_NaGl_SS</ci>
        <apply>
          <times />
          <apply>
            <minus />
            <ci>F</ci>
          </apply>
          <apply>
            <plus />
            <apply>
              <times />
              <ci>z_c</ci>
              <apply>
                <minus />
                <apply>
                  <times />
                  <ci>k_16</ci>
                  <ci>C1</ci>
                </apply>
                <apply>
                  <times />
                  <ci>k_61</ci>
                  <ci>C6</ci>
                </apply>
              </apply>
            </apply>
            <apply>
              <times />
              <apply>
                <plus />
                <ci>z_c</ci>
                <apply>
                  <times />
                  <ci>z_Na</ci>
                  <ci>n</ci>
                </apply>
              </apply>
              <apply>
                <minus />
                <apply>
                  <times />
                  <ci>k_25</ci>
                  <ci>C2</ci>
                </apply>
                <apply>
                  <times />
                  <ci>k_52</ci>
                  <ci>C5</ci>
                </apply>
              </apply>
            </apply>
            <apply>
              <times />
              <apply>
                <plus />
                <ci>z_c</ci>
                <apply>
                  <times />
                  <ci>z_Na</ci>
                  <ci>n</ci>
                </apply>
              </apply>
              <apply>
                <minus />
                <apply>
                  <times />
                  <ci>k_34</ci>
                  <ci>C3</ci>
                </apply>
                <apply>
                  <times />
                  <ci>k_43</ci>
                  <ci>C4</ci>
                </apply>
              </apply>
            </apply>
          </apply>
        </apply>
      </apply>
    </math>
  </component>
  <component name="phenomonological_constants">
    <variable cmeta:id="phenomonological_constants.epsilon" name="epsilon" public_interface="out" units="per_second" />
    <variable cmeta:id="phenomonological_constants.lambda" name="lambda" public_interface="out" units="per_M3_per_second5" />
    <variable cmeta:id="phenomonological_constants.chi" name="chi" public_interface="out" units="M" />
    <variable cmeta:id="phenomonological_constants.alpha" name="alpha" public_interface="out" units="M3" />
    <variable cmeta:id="phenomonological_constants.beta" name="beta" public_interface="out" units="M2" />
    <variable cmeta:id="phenomonological_constants.gamma" name="gamma" public_interface="out" units="M3_per_second" />
    <variable cmeta:id="phenomonological_constants.phi" name="phi" public_interface="out" units="M_per_second" />
    <variable cmeta:id="phenomonological_constants.k_12" name="k_12" public_interface="in" units="per_second" />
    <variable cmeta:id="phenomonological_constants.k_21" name="k_21" public_interface="in" units="per_second" />
    <variable cmeta:id="phenomonological_constants.k_23" name="k_23" public_interface="in" units="per_second" />
    <variable cmeta:id="phenomonological_constants.k_32" name="k_32" public_interface="in" units="per_second" />
    <variable cmeta:id="phenomonological_constants.k_34" name="k_34" public_interface="in" units="per_second" />
    <variable cmeta:id="phenomonological_constants.k_43" name="k_43" public_interface="in" units="per_second" />
    <variable cmeta:id="phenomonological_constants.k_45" name="k_45" public_interface="in" units="per_second" />
    <variable cmeta:id="phenomonological_constants.k_54" name="k_54" public_interface="in" units="per_second" />
    <variable cmeta:id="phenomonological_constants.k_25" name="k_25" public_interface="in" units="per_second" />
    <variable cmeta:id="phenomonological_constants.k_52" name="k_52" public_interface="in" units="per_second" />
    <variable cmeta:id="phenomonological_constants.k_56" name="k_56" public_interface="in" units="per_second" />
    <variable cmeta:id="phenomonological_constants.k_65" name="k_65" public_interface="in" units="per_second" />
    <variable cmeta:id="phenomonological_constants.k_61" name="k_61" public_interface="in" units="per_second" />
    <variable cmeta:id="phenomonological_constants.k_16" name="k_16" public_interface="in" units="per_second" />
    <variable cmeta:id="phenomonological_constants.ks_12" name="ks_12" public_interface="in" units="per_M2_per_second" />
    <variable cmeta:id="phenomonological_constants.k0_23" name="k0_23" public_interface="in" units="per_M_per_second" />
    <variable cmeta:id="phenomonological_constants.C_T" name="C_T" public_interface="in" units="umol" />
    <variable cmeta:id="phenomonological_constants.F" name="F" public_interface="in" units="C_per_mol" />
    <variable cmeta:id="phenomonological_constants.Na_o" name="Na_o" public_interface="in" units="M" />
    <variable cmeta:id="phenomonological_constants.glucose_o" name="glucose_o" public_interface="in" units="M" />
    <variable cmeta:id="phenomonological_constants.Imax_Na" name="Imax_Na" public_interface="out" units="uA" />
    <variable cmeta:id="phenomonological_constants.Imax_gluc" name="Imax_gluc" public_interface="out" units="uA" />
    <variable cmeta:id="phenomonological_constants.Khalf_Na_sq" name="Khalf_Na_sq" public_interface="out" units="M2" />
    <variable cmeta:id="phenomonological_constants.Khalf_Na" name="Khalf_Na" public_interface="out" units="M" />
    <variable cmeta:id="phenomonological_constants.Khalf_gluc" name="Khalf_gluc" public_interface="out" units="M" />
    <math xmlns="http://www.w3.org/1998/Math/MathML">
      <apply>
        <eq />
        <ci>lambda</ci>
        <apply>
          <plus />
          <apply>
            <times />
            <ci>ks_12</ci>
            <ci>k0_23</ci>
            <ci>k_43</ci>
            <ci>k_54</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>ks_12</ci>
            <ci>k0_23</ci>
            <ci>k_34</ci>
            <ci>k_54</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>ks_12</ci>
            <ci>k0_23</ci>
            <ci>k_45</ci>
            <ci>k_52</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>ks_12</ci>
            <ci>k0_23</ci>
            <ci>k_43</ci>
            <ci>k_52</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>ks_12</ci>
            <ci>k0_23</ci>
            <ci>k_34</ci>
            <ci>k_52</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>ks_12</ci>
            <ci>k0_23</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_65</ci>
          </apply>
          <apply>
            <times />
            <ci>ks_12</ci>
            <ci>k0_23</ci>
            <ci>k_45</ci>
            <ci>k_56</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>ks_12</ci>
            <ci>k0_23</ci>
            <ci>k_43</ci>
            <ci>k_56</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>ks_12</ci>
            <ci>k0_23</ci>
            <ci>k_34</ci>
            <ci>k_56</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>ks_12</ci>
            <ci>k0_23</ci>
            <ci>k_43</ci>
            <ci>k_54</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>ks_12</ci>
            <ci>k0_23</ci>
            <ci>k_34</ci>
            <ci>k_54</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>ks_12</ci>
            <ci>k0_23</ci>
            <ci>k_45</ci>
            <ci>k_52</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>ks_12</ci>
            <ci>k0_23</ci>
            <ci>k_43</ci>
            <ci>k_52</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>ks_12</ci>
            <ci>k0_23</ci>
            <ci>k_34</ci>
            <ci>k_52</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>ks_12</ci>
            <ci>k0_23</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_61</ci>
          </apply>
          <apply>
            <times />
            <ci>ks_12</ci>
            <ci>k0_23</ci>
            <ci>k_34</ci>
            <ci>k_45</ci>
            <ci>k_56</ci>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>chi</ci>
        <apply>
          <times />
          <apply>
            <divide />
            <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
            <ci>lambda</ci>
          </apply>
          <apply>
            <plus />
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_32</ci>
              <ci>k_43</ci>
              <ci>k_54</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_25</ci>
              <ci>k_43</ci>
              <ci>k_54</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_25</ci>
              <ci>k_34</ci>
              <ci>k_54</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_25</ci>
              <ci>k_32</ci>
              <ci>k_54</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_34</ci>
              <ci>k_45</ci>
              <ci>k_52</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_32</ci>
              <ci>k_45</ci>
              <ci>k_52</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_32</ci>
              <ci>k_43</ci>
              <ci>k_52</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_25</ci>
              <ci>k_34</ci>
              <ci>k_45</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_25</ci>
              <ci>k_32</ci>
              <ci>k_45</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_25</ci>
              <ci>k_32</ci>
              <ci>k_43</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_34</ci>
              <ci>k_45</ci>
              <ci>k_56</ci>
              <ci>k_61</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_32</ci>
              <ci>k_45</ci>
              <ci>k_56</ci>
              <ci>k_61</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_32</ci>
              <ci>k_43</ci>
              <ci>k_56</ci>
              <ci>k_61</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_32</ci>
              <ci>k_43</ci>
              <ci>k_54</ci>
              <ci>k_61</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_25</ci>
              <ci>k_43</ci>
              <ci>k_54</ci>
              <ci>k_61</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_25</ci>
              <ci>k_34</ci>
              <ci>k_54</ci>
              <ci>k_61</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_25</ci>
              <ci>k_32</ci>
              <ci>k_54</ci>
              <ci>k_61</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_34</ci>
              <ci>k_45</ci>
              <ci>k_52</ci>
              <ci>k_61</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_32</ci>
              <ci>k_45</ci>
              <ci>k_52</ci>
              <ci>k_61</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_32</ci>
              <ci>k_43</ci>
              <ci>k_52</ci>
              <ci>k_61</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_25</ci>
              <ci>k_34</ci>
              <ci>k_45</ci>
              <ci>k_61</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_25</ci>
              <ci>k_32</ci>
              <ci>k_45</ci>
              <ci>k_61</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_25</ci>
              <ci>k_32</ci>
              <ci>k_43</ci>
              <ci>k_61</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_25</ci>
              <ci>k_34</ci>
              <ci>k_45</ci>
              <ci>k_56</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_25</ci>
              <ci>k_32</ci>
              <ci>k_45</ci>
              <ci>k_56</ci>
            </apply>
            <apply>
              <times />
              <ci>ks_12</ci>
              <ci>k_25</ci>
              <ci>k_32</ci>
              <ci>k_43</ci>
              <ci>k_56</ci>
            </apply>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>beta</ci>
        <apply>
          <times />
          <apply>
            <divide />
            <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
            <ci>lambda</ci>
          </apply>
          <apply>
            <plus />
            <apply>
              <times />
              <ci>k0_23</ci>
              <ci>k_16</ci>
              <ci>k_43</ci>
              <ci>k_54</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k0_23</ci>
              <ci>k_16</ci>
              <ci>k_34</ci>
              <ci>k_54</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k0_23</ci>
              <ci>k_16</ci>
              <ci>k_45</ci>
              <ci>k_52</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k0_23</ci>
              <ci>k_16</ci>
              <ci>k_43</ci>
              <ci>k_52</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k0_23</ci>
              <ci>k_16</ci>
              <ci>k_34</ci>
              <ci>k_52</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k0_23</ci>
              <ci>k_16</ci>
              <ci>k_34</ci>
              <ci>k_45</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k0_23</ci>
              <ci>k_34</ci>
              <ci>k_45</ci>
              <ci>k_56</ci>
              <ci>k_61</ci>
            </apply>
            <apply>
              <times />
              <ci>k0_23</ci>
              <ci>k_16</ci>
              <ci>k_34</ci>
              <ci>k_45</ci>
              <ci>k_56</ci>
            </apply>
          </apply>
        </apply>
      </apply>
      <apply>
        <eq />
        <ci>alpha</ci>
        <apply>
          <times />
          <apply>
            <divide />
            <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
            <ci>lambda</ci>
          </apply>
          <apply>
            <plus />
            <apply>
              <times />
              <ci>k_21</ci>
              <ci>k_32</ci>
              <ci>k_43</ci>
              <ci>k_54</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k_16</ci>
              <ci>k_32</ci>
              <ci>k_43</ci>
              <ci>k_54</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k_16</ci>
              <ci>k_25</ci>
              <ci>k_43</ci>
              <ci>k_54</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k_16</ci>
              <ci>k_21</ci>
              <ci>k_43</ci>
              <ci>k_54</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k_16</ci>
              <ci>k_25</ci>
              <ci>k_34</ci>
              <ci>k_54</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k_16</ci>
              <ci>k_21</ci>
              <ci>k_34</ci>
              <ci>k_54</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k_16</ci>
              <ci>k_25</ci>
              <ci>k_32</ci>
              <ci>k_54</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k_16</ci>
              <ci>k_21</ci>
              <ci>k_32</ci>
              <ci>k_54</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k_21</ci>
              <ci>k_34</ci>
              <ci>k_45</ci>
              <ci>k_52</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k_16</ci>
              <ci>k_34</ci>
              <ci>k_45</ci>
              <ci>k_52</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k_21</ci>
              <ci>k_32</ci>
              <ci>k_45</ci>
              <ci>k_52</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k_16</ci>
              <ci>k_32</ci>
              <ci>k_45</ci>
              <ci>k_52</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k_21</ci>
              <ci>k_32</ci>
              <ci>k_43</ci>
              <ci>k_52</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k_16</ci>
              <ci>k_32</ci>
              <ci>k_43</ci>
              <ci>k_52</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k_16</ci>
              <ci>k_25</ci>
              <ci>k_34</ci>
              <ci>k_45</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k_16</ci>
              <ci>k_21</ci>
              <ci>k_34</ci>
              <ci>k_45</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k_16</ci>
              <ci>k_25</ci>
              <ci>k_32</ci>
              <ci>k_45</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k_16</ci>
              <ci>k_21</ci>
              <ci>k_32</ci>
              <ci>k_45</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k_16</ci>
              <ci>k_25</ci>
              <ci>k_32</ci>
              <ci>k_43</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k_16</ci>
              <ci>k_21</ci>
              <ci>k_32</ci>
              <ci>k_43</ci>
              <ci>k_65</ci>
            </apply>
            <apply>
              <times />
              <ci>k_25</ci>
              <ci>k_34</ci>
              <ci>k_45</ci>
              <ci>k_56</ci>
              <ci>k_61</ci>
            </apply>
            <apply>
              <times />
              <ci>k_21</ci>
              <ci>k_34</ci>
              <ci>k_45</ci>
              <ci>k_56</ci>
              <ci>k_61</ci>
            </apply>
            <apply>
              <times />
              <ci>k_25</ci>
              <ci>k_32</ci>
              <ci>k_45</ci>
              <ci>k_56</ci>
              <ci>k_61</ci>
            </apply>
            <apply>
              <times />
              <ci>k_21</ci>
              <ci>k_32</ci>
              <ci>k_45</ci>
              <ci>k_56</ci>
              <ci>k_61</ci>
            </apply>
            <apply>
              <times />
              <ci>k_25</ci>
              <ci>k_32</ci>
              <ci>k_43</ci>
              <ci>k_56</ci>
              <ci>k_61</ci>
            </apply>
            <apply>
              <times />
              <ci>k_21</ci>
              <ci>k_32</ci>
              <ci>k_43</ci>
              <ci>k_56</ci>
              <ci>k_61</ci>
            </apply>
            <apply>
              <times />
              <ci>k_21</ci>
              <ci>k_32</ci>
              <ci>k_43</ci>
              <ci>k_54</ci>
              <ci>k_61</ci>
            </apply>
            <apply>
              <times />
              <ci>k_21</ci>
              <ci>k_34</ci>
              <ci>k_45</ci>
              <ci>k_52</ci>
              <ci>k_61</ci>
            </apply>
            <apply>
              <times />
              <ci>k_21</ci>
              <ci>k_32</ci>
              <ci>k_45</ci>
              <ci>k_52</ci>
              <ci>k_61</ci>
            </apply>
            <apply>
              <times />
              <ci>k_21</ci>
              <ci>k_32</ci>
              <ci>k_43</ci>
              <ci>k_52</ci>
              <ci>k_61</ci>
            </apply>
            <apply>
              <times />
              <ci>k_16</ci>
              <ci>k_25</ci>
              <ci>k_34</ci>
              <ci>k_45</ci>
              <ci>k_56</ci>
            </apply>
            <apply>
              <times />
              <ci>k_16</ci>
              <ci>k_21</ci>
              <ci>k_34</ci>
              <ci>k_45</ci>
              <ci>k_56</ci>
            </apply>
            <apply>
              <times />
              <ci>k_16</ci>
              <ci>k_25</ci>
              <ci>k_32</ci>
              <ci>k_45</ci>
              <ci>k_56</ci>
            </apply>
            <apply>
              <times />
              <ci>k_16</ci>
              <ci>k_21</ci>
              <ci>k_32</ci>
              <ci>k_45</ci>
              <ci>k_56</ci>
            </apply>
            <apply>
              <times />
              <ci>k_16</ci>
              <ci>k_25</ci>
              <ci>k_32</ci>
              <ci>k_43</ci>
              <ci>k_56</ci>
            </apply>
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      <dcterms:title>Kinetics of the Reverse Mode of the Na+/Glucose Cotransporter</dcterms:title>
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      <dcterms:abstract>This study investigates the reverse mode of the Na/glucose cotransporter (SGLT1). In giant excised inside-out membrane patches from Xenopus laevis oocytes expressing rabbit SGLT1, application of a-methyl-D-glucopyranoside (aMDG) to the cytoplasmic solution induced an outward current from cytosolic to external membrane surface. The outward current was Na- and sugar-dependent, and was blocked by phlorizin, a specific inhibitor of SGLT1. The current-voltage relationship saturated at positive membrane voltages (30-50 mV), and approached zero at -150 mV. The half-maximal concentration for aMDG-evoked outward current (K_0.5_aMDG) was 35 mM (at 0 mV). In comparison, K_0.5_aMDG for forward sugar transport was 0.15 mM (at 0 mV). K_0.5_Na was similar for forward and reverse transport (~ 35mM at 0 mV). Specificity of SGLT1 for reverse transport was: aMDG (1.0) &gt; D-galactose (0.84) &gt; 3-O-methyl-glucose (0.55) &gt; D-glucose (0.38), whereas for forward transport, specificity was: aMDG ~ D-glucose ~ D-galactose &gt; 3-O-methylglucose. Thus there is an asymmetry in sugar kinetics and specificity between forward and reverse modes. Computer simulations showed that a 6-state kinetic model for SGLT1 can account for Na/sugar cotransport and its voltage dependence in both the forward and reverse modes at saturating sodium concentrations. Our data indicate that under physiological conditions, the transporter is poised to accumulate sugar efficiently in the enterocyte.</dcterms:abstract>
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      <semsim:unknown>This study investigates the reverse mode of the Na/glucose cotransporter (SGLT1). In giant excised inside-out membrane patches from Xenopus laevis oocytes expressing rabbit SGLT1, application of a-methyl-D-glucopyranoside (aMDG) to the cytoplasmic solution induced an outward current from cytosolic to external membrane surface. The outward current was Na- and sugar-dependent, and was blocked by phlorizin, a specific inhibitor of SGLT1. The current-voltage relationship saturated at positive membrane voltages (30-50 mV), and approached zero at -150 mV. The half-maximal concentration for aMDG-evoked outward current (K_0.5_aMDG) was 35 mM (at 0 mV). In comparison, K_0.5_aMDG for forward sugar transport was 0.15 mM (at 0 mV). K_0.5_Na was similar for forward and reverse transport (~ 35mM at 0 mV). Specificity of SGLT1 for reverse transport was: aMDG (1.0) &gt; D-galactose (0.84) &gt; 3-O-methyl-glucose (0.55) &gt; D-glucose (0.38), whereas for forward transport, specificity was: aMDG ~ D-glucose ~ D-galactose &gt; 3-O-methylglucose. Thus there is an asymmetry in sugar kinetics and specificity between forward and reverse modes. Computer simulations showed that a 6-state kinetic model for SGLT1 can account for Na/sugar cotransport and its voltage dependence in both the forward and reverse modes at saturating sodium concentrations. Our data indicate that under physiological conditions, the transporter is poised to accumulate sugar efficiently in the enterocyte.</semsim:unknown>
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