- Author:
- Catherine Lloyd <c.lloyd@auckland.ac.nz>
- Date:
- 2010-04-20 12:25:51+12:00
- Desc:
- Added documentation and metadata. Needs curation comment to be updated.
- Permanent Source URI:
- https://models.physiomeproject.org/workspace/gross_and_hopfer_1999/rawfile/1a9f55d693973de360933f0b44867b6d77ffa197/gross_and_hopfer_1999.cellml
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COR (0.9.31.1265)
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http://COR.physiol.ox.ac.uk/ - COR@physiol.ox.ac.uk
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http://www.CellML.org/
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<title>Effects of pH on kinetic parameters of the Na-HCO3 cotransporter in renal proximal tubule</title>
<author>
<firstname>Jonna</firstname>
<surname>Terkildsen</surname>
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<shortaffil>Auckland Bioengineering Institute, University of Auckland</shortaffil>
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This CellML model..........................................
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ABSTRACT: The effects of pH on cotransporter kinetics were studied in renal proximal tubule cells. Cells were grown to confluence on permeable support, mounted in an Ussing-type chamber, and permeabilized apically to small monovalent ions with amphotericin B. The steady-state, dinitrostilbene-disulfonate-sensitive current (DeltaI) was Na+ and HCO3- dependent and therefore was taken as flux through the cotransporter. When the pH of the perfusing solution was changed between 6.0 and 8.0, the conductance attributable to the cotransporter showed a maximum between pH 7.25 and pH 7.50. A similar profile was observed in the presence of a pH gradient when the pH of the apical solutions was varied between 7.0 and 8.0 (basal pH lower by 1), but not when the pH of the basal solution was varied between 7.0 and 8.0 (apical pH lower by 1 unit). To delineate the kinetic basis for these observations, DeltaI-voltage curves were obtained as a function of Na+ and HCO3- concentrations and analyzed on the basis of a kinetic cotransporter model. Increases in pH from 7.0 to 8.0 decreased the binding constants for the intracellular and extracellular substrates by a factor of 2. Furthermore, the electrical parameters that describe the interaction strength between the electric field and substrate binding or charge on the unloaded transporter increased by four- to fivefold. These data can be explained by a channel-like structure of the cotransporter, whose configuration is modified by intracellular pH such that, with increasing pH, binding of substrate to the carrier is sterically hindered but electrically facilitated.
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<para>
The original paper reference is cited below:
</para>
<para>
Effects of pH on kinetic parameters of the Na-HCO3 cotransporter in renal proximal tubule, E. Gross and U. Hopfer, 1999,
<emphasis>Biophysical Journal</emphasis>, 76, 3066-3075. <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/10354432">PubMed ID: 10354432</ulink>
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<caption>A six-state ordered-binding transport model of the Na-HCO3 cotransporter. The binding of three HCO3- anions to the carrier is described as a single, lumped step.</caption>
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</bvar>
<ci>C_4</ci>
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<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci>f_3</ci>
<ci>C_3</ci>
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<apply>
<times/>
<ci>b_4</ci>
<ci>C_5</ci>
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<apply>
<times/>
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<plus/>
<ci>b_3</ci>
<ci>f_4</ci>
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<ci>C_4</ci>
</apply>
</apply>
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<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C_5</ci>
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<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci>f_4</ci>
<ci>C_4</ci>
</apply>
<apply>
<times/>
<ci>b_5</ci>
<ci>C_6</ci>
</apply>
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<apply>
<times/>
<apply>
<plus/>
<ci>b_4</ci>
<ci>f_5</ci>
</apply>
<ci>C_5</ci>
</apply>
</apply>
</apply>
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C_6_temp</ci>
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<apply>
<minus/>
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<plus/>
<apply>
<times/>
<ci>f_5</ci>
<ci>C_5</ci>
</apply>
<apply>
<times/>
<ci>b_6</ci>
<ci>C_1</ci>
</apply>
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<apply>
<times/>
<apply>
<plus/>
<ci>b_5</ci>
<ci>f_6</ci>
</apply>
<ci>C_6</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>
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<variable name="f_1" units="per_second" public_interface="in"/>
<variable name="b_1" units="per_second" public_interface="in"/>
<variable name="f_2" units="per_second" public_interface="in"/>
<variable name="b_2" units="per_second" public_interface="in"/>
<variable name="f_3" units="per_second" public_interface="in"/>
<variable name="b_3" units="per_second" public_interface="in"/>
<variable name="f_4" units="per_second" public_interface="in"/>
<variable name="b_4" units="per_second" public_interface="in"/>
<variable name="f_5" units="per_second" public_interface="in"/>
<variable name="b_5" units="per_second" public_interface="in"/>
<variable name="f_6" units="per_second" public_interface="in"/>
<variable name="b_6" units="per_second" public_interface="in"/>
<variable name="C1_sum" units="per_second5"/>
<variable name="C2_sum" units="per_second5"/>
<variable name="C3_sum" units="per_second5"/>
<variable name="C4_sum" units="per_second5"/>
<variable name="C5_sum" units="per_second5"/>
<variable name="C6_sum" units="per_second5"/>
<variable name="C_sum" units="per_second5"/>
<variable name="C_T" units="pmol_per_cm2" public_interface="in"/>
<variable name="C1" units="pmol_per_cm2" public_interface="out"/>
<variable name="C2" units="pmol_per_cm2" public_interface="out"/>
<variable name="C3" units="pmol_per_cm2" public_interface="out"/>
<variable name="C4" units="pmol_per_cm2" public_interface="out"/>
<variable name="C5" units="pmol_per_cm2" public_interface="out"/>
<variable name="C6" units="pmol_per_cm2" public_interface="out"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
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<eq/>
<ci>C1_sum</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>f_2</ci>
<ci>f_3</ci>
<ci>f_4</ci>
<ci>f_5</ci>
<ci>f_6</ci>
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<times/>
<ci>b_1</ci>
<ci>f_3</ci>
<ci>f_4</ci>
<ci>f_5</ci>
<ci>f_6</ci>
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<times/>
<ci>b_1</ci>
<ci>b_2</ci>
<ci>f_4</ci>
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<ci>f_6</ci>
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<times/>
<ci>b_1</ci>
<ci>b_2</ci>
<ci>b_3</ci>
<ci>f_5</ci>
<ci>f_6</ci>
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<times/>
<ci>b_1</ci>
<ci>b_2</ci>
<ci>b_3</ci>
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<times/>
<ci>b_1</ci>
<ci>b_2</ci>
<ci>b_3</ci>
<ci>b_4</ci>
<ci>b_5</ci>
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<apply>
<eq/>
<ci>C2_sum</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>f_1</ci>
<ci>f_3</ci>
<ci>f_4</ci>
<ci>f_5</ci>
<ci>f_6</ci>
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<times/>
<ci>b_2</ci>
<ci>f_1</ci>
<ci>f_4</ci>
<ci>f_5</ci>
<ci>f_6</ci>
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<times/>
<ci>b_2</ci>
<ci>b_3</ci>
<ci>f_1</ci>
<ci>f_5</ci>
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<times/>
<ci>b_2</ci>
<ci>b_3</ci>
<ci>b_4</ci>
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<times/>
<ci>b_2</ci>
<ci>b_3</ci>
<ci>b_4</ci>
<ci>b_5</ci>
<ci>f_1</ci>
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<times/>
<ci>b_2</ci>
<ci>b_3</ci>
<ci>b_4</ci>
<ci>b_5</ci>
<ci>b_6</ci>
</apply>
</apply>
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<apply>
<eq/>
<ci>C3_sum</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>f_1</ci>
<ci>f_2</ci>
<ci>f_4</ci>
<ci>f_5</ci>
<ci>f_6</ci>
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<apply>
<times/>
<ci>b_3</ci>
<ci>f_1</ci>
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<ci>f_5</ci>
<ci>f_6</ci>
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<times/>
<ci>b_3</ci>
<ci>b_4</ci>
<ci>f_1</ci>
<ci>f_2</ci>
<ci>f_6</ci>
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<times/>
<ci>b_3</ci>
<ci>b_4</ci>
<ci>b_5</ci>
<ci>f_1</ci>
<ci>f_2</ci>
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<times/>
<ci>b_3</ci>
<ci>b_4</ci>
<ci>b_5</ci>
<ci>b_6</ci>
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<times/>
<ci>b_1</ci>
<ci>b_3</ci>
<ci>b_4</ci>
<ci>b_5</ci>
<ci>b_6</ci>
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<apply>
<eq/>
<ci>C4_sum</ci>
<apply>
<plus/>
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<times/>
<ci>f_1</ci>
<ci>f_2</ci>
<ci>f_3</ci>
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<times/>
<ci>b_4</ci>
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<ci>f_6</ci>
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<times/>
<ci>b_4</ci>
<ci>b_5</ci>
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<ci>f_3</ci>
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<times/>
<ci>b_4</ci>
<ci>b_5</ci>
<ci>b_6</ci>
<ci>f_2</ci>
<ci>f_3</ci>
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<times/>
<ci>b_1</ci>
<ci>b_4</ci>
<ci>b_5</ci>
<ci>b_6</ci>
<ci>f_3</ci>
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<times/>
<ci>b_1</ci>
<ci>b_2</ci>
<ci>b_4</ci>
<ci>b_5</ci>
<ci>b_6</ci>
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<apply>
<eq/>
<ci>C5_sum</ci>
<apply>
<plus/>
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<times/>
<ci>f_1</ci>
<ci>f_2</ci>
<ci>f_3</ci>
<ci>f_4</ci>
<ci>f_6</ci>
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<times/>
<ci>b_5</ci>
<ci>f_1</ci>
<ci>f_2</ci>
<ci>f_3</ci>
<ci>f_4</ci>
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<times/>
<ci>b_5</ci>
<ci>b_6</ci>
<ci>f_2</ci>
<ci>f_3</ci>
<ci>f_4</ci>
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<times/>
<ci>b_1</ci>
<ci>b_5</ci>
<ci>b_6</ci>
<ci>f_3</ci>
<ci>f_4</ci>
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<times/>
<ci>b_1</ci>
<ci>b_2</ci>
<ci>b_5</ci>
<ci>b_6</ci>
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<times/>
<ci>b_1</ci>
<ci>b_2</ci>
<ci>b_3</ci>
<ci>b_5</ci>
<ci>b_6</ci>
</apply>
</apply>
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<apply>
<eq/>
<ci>C6_sum</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>f_1</ci>
<ci>f_2</ci>
<ci>f_3</ci>
<ci>f_4</ci>
<ci>f_5</ci>
</apply>
<apply>
<times/>
<ci>b_6</ci>
<ci>f_2</ci>
<ci>f_3</ci>
<ci>f_4</ci>
<ci>f_5</ci>
</apply>
<apply>
<times/>
<ci>b_1</ci>
<ci>b_6</ci>
<ci>f_3</ci>
<ci>f_4</ci>
<ci>f_5</ci>
</apply>
<apply>
<times/>
<ci>b_1</ci>
<ci>b_2</ci>
<ci>b_6</ci>
<ci>f_4</ci>
<ci>f_5</ci>
</apply>
<apply>
<times/>
<ci>b_1</ci>
<ci>b_2</ci>
<ci>b_3</ci>
<ci>b_6</ci>
<ci>f_5</ci>
</apply>
<apply>
<times/>
<ci>b_1</ci>
<ci>b_2</ci>
<ci>b_3</ci>
<ci>b_4</ci>
<ci>b_6</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 xmlns="http://www.cellml.org/cellml/1.0#" name="NBC_current">
<variable name="f_3" units="per_second" public_interface="in"/>
<variable name="b_3" units="per_second" public_interface="in"/>
<variable name="f_6" units="per_second" public_interface="in"/>
<variable name="b_6" units="per_second" public_interface="in"/>
<variable name="C_1" units="pmol_per_cm2" public_interface="in"/>
<variable name="C_3" units="pmol_per_cm2" public_interface="in"/>
<variable name="C_4" units="pmol_per_cm2" public_interface="in"/>
<variable name="C_6" units="pmol_per_cm2" public_interface="in"/>
<variable name="C1" units="pmol_per_cm2" public_interface="in"/>
<variable name="C3" units="pmol_per_cm2" public_interface="in"/>
<variable name="C4" units="pmol_per_cm2" public_interface="in"/>
<variable name="C6" units="pmol_per_cm2" public_interface="in"/>
<variable name="delta_z" units="dimensionless" public_interface="in"/>
<variable name="n" units="dimensionless" public_interface="in"/>
<variable name="m" units="dimensionless" public_interface="in"/>
<variable name="F" units="C_per_mmol" public_interface="in"/>
<variable name="I_NBC" units="nA_per_cm2" public_interface="out"/>
<variable name="I_NBC_SS" units="nA_per_cm2" public_interface="out"/>
<variable name="I_NBC_micro" units="uA_per_cm2" public_interface="out"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>I_NBC</ci>
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<times/>
<apply>
<minus/>
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<minus/>
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<ci>b_6</ci>
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<ci>f_6</ci>
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<minus/>
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<plus/>
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<apply>
<minus/>
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<times/>
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<apply>
<eq/>
<ci>I_NBC_micro</ci>
<apply>
<times/>
<cn type="e-notation" cellml:units="uA_per_nA">1 <sep/>
-3</cn>
<apply>
<minus/>
<ci>F</ci>
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<plus/>
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<times/>
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<apply>
<minus/>
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<ci>b_6</ci>
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<minus/>
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<plus/>
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<apply>
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<ci>I_NBC_SS</ci>
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<times/>
<apply>
<minus/>
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<minus/>
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<times/>
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<minus/>
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<plus/>
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<apply>
<minus/>
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<times/>
<ci>f_3</ci>
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<apply>
<times/>
<ci>b_3</ci>
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</math>
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<map_variables variable_1="HCO3_i" variable_2="HCO3_i"/>
<map_variables variable_1="HCO3_o" variable_2="HCO3_o"/>
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<map_components component_1="rate_constants" component_2="king_altman_states"/>
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<connection xmlns="http://www.cellml.org/cellml/1.0#">
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<connection xmlns="http://www.cellml.org/cellml/1.0#">
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<map_variables variable_1="F" variable_2="F"/>
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<connection xmlns="http://www.cellml.org/cellml/1.0#">
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<connection xmlns="http://www.cellml.org/cellml/1.0#">
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<map_variables variable_1="C4" variable_2="C4"/>
<map_variables variable_1="C6" variable_2="C6"/>
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<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="kinetic_equations" component_2="environment"/>
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<connection xmlns="http://www.cellml.org/cellml/1.0#">
<map_components component_1="kinetic_equations" component_2="parameters"/>
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<connection xmlns="http://www.cellml.org/cellml/1.0#">
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Effects of pH on kinetic parameters of the Na-HCO3 cotransporter in renal proximal tubule
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