A mathematical model of the pancreatic ductal epithelium.
A mathematical model of the HCO-3-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/HCO-3-free, HEPES-buffered solution, and also the intracellular pH of duct cells bathed in a CO2/HCO-3-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 HCO-3 secretory rate and intracellular pH during HCO-3 secretion. We believe that the model will be helpful in the analysis of experimental data and improve our understanding of HCO-3-transporting mechanisms in pancreatic duct cells.
Sohma
Y
Y
Department of Physiological Sciences, University Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
Gray
M A
MA
Imai
Y
Y
Argent
B E
BE
D000818:Animals; D004848:Epithelium / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport; D008564:Membrane Potentials; D008962:Models, Theoretical; D010179:Pancreas / Q000502:physiology*