TY - JOUR

T1 - A mathematical model of the pancreatic ductal epithelium

AU - Sohma, Y.

AU - Gray, M. A.

AU - Imai, Y.

AU - Argent, B. E.

PY - 1996

Y1 - 1996

N2 - 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.

AB - 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.

KW - Cystic fibrosis transmembrane conductance regulator

KW - HCO secretion

KW - Intracellular pH regulation

KW - Mathematical model

KW - Pancreatic duct

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UR - http://www.scopus.com/inward/citedby.url?scp=0029851860&partnerID=8YFLogxK

U2 - 10.1007/s002329900132

DO - 10.1007/s002329900132

M3 - Article

C2 - 8881027

AN - SCOPUS:0029851860

SN - 0022-2631

VL - 154

SP - 53

EP - 67

JO - Journal of Membrane Biology

JF - Journal of Membrane Biology

IS - 1

ER -