Apical Cl-/HCO3- exchanger stoichiometry in the modeling of HCO3- transport by pancreatic duct epithelium.
Pancreatic duct cells secrete a HCO(3)(-)-rich (approximately 140 mM) fluid. Using a computer model of the pancreatic duct, Sohma, et al. have demonstrated that the activity of a Cl(-)/HCO(3)(-) exchanger with a 1: 1 stoichiometry at the apical membrane would have to be suppressed in order to achieve such a HCO(3)(-)-rich secretion. Recently the apical exchanger in pancreatic ducts has been identified as SLC26A6 and this probably mediates most of Cl(-)-dependent HCO(3)(-) secretion across the apical membrane. SLC26A6 is reported to mediate electrogenic Cl(-)/2HCO(3)(-) exchange when expressed in Xenopus oocytes. To assess the implications of this 1: 2 stoichiometry for HCO(3)(-) secretion, we have reconstructed the Sohma model using MATLAB/Simulink. To do this we have formulated an expression for the turnover rate of Cl(-)/2HCO(3)(-) 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 HCO(3)(-) secretion at higher concentrations.
Department of Human Nutrition, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Makoto
M
Yamaguchi
Hiroshi
H
Ishiguro
Martin
M
Steward
Yoshiro
Y
Sohma
Akiko
A
Yamamoto
Akito
A
Shimouchi
Takaharu
T
Kondo
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D027963:Chloride-Bicarbonate Antiporters / Q000737:chemistry* / Q000378:metabolism; D003198:Computer Simulation; D004848:Epithelium / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D008954:Models, Biological; D010183:Pancreatic Ducts / Q000378:metabolism*; D014982:Xenopus laevis
D001639:Bicarbonates; D027963:Chloride-Bicarbonate Antiporters