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 (approximately 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 approximately 70 mM), but mainly via channels further down the ductal tree (raising luminal HCO3- to approximately 140 mM).
Sohma
Y
Y
Department of Physiology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
Gray
M A
MA
Imai
Y
Y
Argent
B E
BE
D000818:Animals; D017920:Antiporters / Q000378:metabolism; D001639:Bicarbonates / Q000378:metabolism*; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D027963:Chloride-Bicarbonate Antiporters; D003198:Computer Simulation; D004848:Epithelium / Q000378:metabolism; D008432:Mathematical Computing; D008954:Models, Biological; D010179:Pancreas / Q000378:metabolism*; D017494:Proton Pumps / Q000378:metabolism; D027982:Sodium-Bicarbonate Symporters; D012996:Solutions
D017920:Antiporters; D001639:Bicarbonates; D002352:Carrier Proteins; D027963:Chloride-Bicarbonate Antiporters; D017494:Proton Pumps; D027982:Sodium-Bicarbonate Symporters; D012996:Solutions