A mathematical model of the pancreatic ductal epithelium

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.