A Mathematical Model of the Pancreatic Ductal Epithelium |
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Authors: | Y Sohma MA Gray Y Imai BE Argent |
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Institution: | (1) Department of Physiological Sciences, University Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK, GB;(2) Department of Physiology, Osaka Medical College, Takatsuki Osaka 569, Japan, JP |
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Abstract: | 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.
Received: 18 October 1995/Revised: 5 July 1996 |
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Keywords: | : Pancreatic duct — Mathematical model — HCO− 3 secretion — Intracellular pH regulation — Cystic fibrosis transmembrane conductance regulator |
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