A mathematical model of the HCO3--secreting pancreatic ductal epithelium was developed using network thermodynamics. With a minimal set of assumptions, the model accurately reproduced the experimentally measured membrane potentials, voltage divider ratio, transepithelial resistance and short-circuit current of nonstimulated ducts that were microperfused and bathed with a CO2/HCO3--free, HEPES-buffered solution, and also the intracellular pH of duct cells bathed in a CO2/HCO3--buffered solution. The model also accurately simulated: (i) the effect of step changes in basolateral K+ concentration, and the effect of K+ channel blockers on basolateral membrane potential; (ii) the intracellular acidification caused by a Na+-free extracellular solution and the effect of amiloride on this acidification; and (iii) the intracellular alkalinization caused by a Cl--free extracellular solution and the effect of DIDS on this alkalinization. In addition, the model predicted that the luminal Cl- conductance plays a key role in controlling both the HCO3- secretory rate and intracellular pH during HCO3- secretion. We believe that the model will be helpful in the analysis of experimental data and improve our understanding of HCO3--transporting mechanisms in pancreatic duct cells.
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