The pancreatic duct epithelium in the guinea-pig and many other species secretes HCO3 - at concentrations approaching 150 mM. This cannot be explained by conventional models based upon HCO3 - secretion via an anion exchanger at the luminal membrane because: 1) under these conditions, the Cl- and HCO3 - concentration gradients would favour HCO3 - reabsorption rather than secretion, and 2) the luminal anion exchanger appears to be inhibited by luminal HCO3 - concentrations of 125 mM or more. There may, however, be a sufficiently large electrochemical gradient to drive HCO3 - secretion across the luminal membrane via an anion conductance. In contrast to earlier studies on rat ducts, the membrane potential Em in guinea-pig duct cells does not depolarise appreciably upon stimulation with secretagogues but remains constant at about – 60 mV. Consequently, even with 125 mM or more HCO3 - in the lumen and an estimated 20 mM in the cytoplasm, the electrochemical gradient for HCO3 - will still favour secretion to the lumen. Under the same conditions, the intracellular Cl- concentration drops to very low levels (approximately 7 mM) presumably because, although Cl- may leave freely through the cystic fibrosis transmembrane conductance regulator (CFTR) channels in the luminal membrane, there is no major pathway for Cl- uptake across the basolateral membrane.
Consequently a HCO3 - -rich secretion may arise as a result of the lack of competition from intracellular Cl- for efflux via the anion conductances at the luminal membrane. Whether CFTR, or another anion conductance, provides such a pathway for HCO3 - remains to be seen.
Satoru Naruse, Hiroshi Ishiguro, Jos? I San Rom?n, Maynard Case, Martin C Steward