Apical Cl-/HCO3- exchanger stoichiometry in the modeling of HCO3- transport by pancreatic duct epithelium

  • Yamaguchi Makoto
    Department of Human Nutrition, Nagoya University Graduate School of Medicine
  • Ishiguro Hiroshi
    Department of Human Nutrition, Nagoya University Graduate School of Medicine
  • Steward Martin
    Faculty of Life Sciences, University of Manchester
  • Sohma Yoshiro
    Department of Pharmacology, School of Medicine, Keio University
  • Yamamoto Akiko
    Department of Human Nutrition, Nagoya University Graduate School of Medicine
  • Shimouchi Akito
    Department of Etiology and Pathogenesis, National Cardiovascular Center Research Institute
  • Kondo Takaharu
    Department of Human Nutrition, Nagoya University Graduate School of Medicine

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Abstract

Pancreatic duct cells secrete a HCO3--rich (∼140 mM) fluid. Using a computer model of the pancreatic duct, Sohma, et al. have demonstrated that the activity of a Cl-/HCO3- exchanger with a 1: 1 stoichiometry at the apical membrane would have to be suppressed in order to achieve such a HCO3--rich secretion. Recently the apical exchanger in pancreatic ducts has been identified as SLC26A6 and this probably mediates most of Cl--dependent HCO3- secretion across the apical membrane. SLC26A6 is reported to mediate electrogenic Cl-/2HCO3- exchange when expressed in Xenopus oocytes. To assess the implications of this 1: 2 stoichiometry for HCO3- secretion, we have reconstructed the Sohma model using MATLAB/Simulink. To do this we have formulated an expression for the turnover rate of Cl-/2HCO3- exchange using network thermodynamics and we have estimated the constants from published experimental data. Preliminary data suggest that the 1: 2 stoichiometry of SLC26A6 would favor HCO3- secretion at higher concentrations. J. Med. Invest. 56 Suppl.: 325-328, December, 2009

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