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 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).