HCO3 − Transport in a Mathematical Model of the Pancreatic Ductal Epithelium

HCO3 − Transport in a Mathematical Model of the Pancreatic Ductal Epithelium We have used computer modeling to investigate how pancreatic duct cells can secrete a fluid containing near isotonic (∼140 mm) NaHCO3. Experimental data suggest that NaHCO3 secretion occurs in three steps: (i) accumulation of HCO− 3 across the basolateral membrane of the duct cell by Na(HCO3) n cotransporters, Na+/H+ exchangers and proton pumps; (ii) secretion of HCO− 3 across the luminal membrane on Cl−/HCO− 3 antiporters operating in parallel with Cl− channels; and (iii) diffusion of Na+ through the paracellular pathway. Programming the currently available experimental data into our computer model shows that this mechanism for HCO− 3 secretion is deficient in one important respect. While it can produce a relatively large volume of a HCO− 3-rich fluid, it can only raise the luminal HCO− 3 concentration up to about 70 mm. To achieve secretion of 140 mm NaHCO3 by the model it is necessary to: (i) reduce the conductive Cl− permeability and increase the conductive HCO− 3 permeability of the luminal membrane of the duct cell, and (ii) reduce the activity of the luminal Cl−/HCO− 3 antiporters. Under these conditions most of the HCO− 3 is secreted via a conductive pathway. Based on our data, we propose that HCO− 3 secretion occurs mainly by the antiporter in duct segments near the acini (luminal HCO− 3 concentration up to ∼70 mm), but mainly via channels further down the ductal tree (raising luminal HCO− 3 to ∼140 mm). http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

HCO3 − Transport in a Mathematical Model of the Pancreatic Ductal Epithelium

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Publisher
Springer-Verlag
Copyright
Copyright © Inc. by 2000 Springer-Verlag New York
Subject
Life Sciences; Biochemistry, general; Human Physiology
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/s00232001077
Publisher site
See Article on Publisher Site

Abstract

We have used computer modeling to investigate how pancreatic duct cells can secrete a fluid containing near isotonic (∼140 mm) NaHCO3. Experimental data suggest that NaHCO3 secretion occurs in three steps: (i) accumulation of HCO− 3 across the basolateral membrane of the duct cell by Na(HCO3) n cotransporters, Na+/H+ exchangers and proton pumps; (ii) secretion of HCO− 3 across the luminal membrane on Cl−/HCO− 3 antiporters operating in parallel with Cl− channels; and (iii) diffusion of Na+ through the paracellular pathway. Programming the currently available experimental data into our computer model shows that this mechanism for HCO− 3 secretion is deficient in one important respect. While it can produce a relatively large volume of a HCO− 3-rich fluid, it can only raise the luminal HCO− 3 concentration up to about 70 mm. To achieve secretion of 140 mm NaHCO3 by the model it is necessary to: (i) reduce the conductive Cl− permeability and increase the conductive HCO− 3 permeability of the luminal membrane of the duct cell, and (ii) reduce the activity of the luminal Cl−/HCO− 3 antiporters. Under these conditions most of the HCO− 3 is secreted via a conductive pathway. Based on our data, we propose that HCO− 3 secretion occurs mainly by the antiporter in duct segments near the acini (luminal HCO− 3 concentration up to ∼70 mm), but mainly via channels further down the ductal tree (raising luminal HCO− 3 to ∼140 mm).

Journal

The Journal of Membrane BiologySpringer Journals

Published: Jul 1, 2000

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