Hco3- Transport in a mathematical model of the pancreatic ductal epithelium

Y. Sohma, M. A. Gray, Y. Imai, B. E. Argent

Research output: Contribution to journalArticle

64 Citations (Scopus)

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 HCO3/- across the basolateral membrane of the duct cell by Na(HCO3)(n) cotransporters, Na+/H+ exchangers and proton pumps; (ii) secretion of HCO3/- across the luminal membrane on Cl-/HCO3/- 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 HCO3/- secretion is deficient in one important respect. While it can produce a relatively large volume of a HCO3/--rich fluid, it can only raise the luminal HCO3/- 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 HCO3/- permeability of the luminal membrane of the duct cell, and (ii) reduce the activity of the luminal Cl-/HCO3/- antiporters. Under these conditions most of the HCO3/- is secreted via a conductive pathway. Based on our data, we propose that HCO3/- secretion occurs mainly by the antiporter in duct segments near the acini (luminal HCO3/- concentration up to (~70 mM), but mainly via channels further down the ductal tree (raising luminal HCO3/- to ~140 mM).

Original languageEnglish
Pages (from-to)77-100
Number of pages24
JournalJournal of Membrane Biology
Volume176
Issue number1
DOIs
Publication statusPublished - 2000 Jul 1

    Fingerprint

Keywords

  • Cl secretion
  • Cystic fibrosis transmembrane conductance regulator
  • HCO/ secretion
  • Mathematical model
  • Pancreatic duct cells

ASJC Scopus subject areas

  • Biophysics
  • Physiology
  • Cell Biology

Cite this