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Address correspondence to Hiroshi Ishiguro, Internal Medicine II, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Fax: (81) 52-744-2179; E-mail: ishiguro@htc.nagoya-u.ac.jp
The interlobular duct cells of the guinea-pig pancreas secrete HCO3- across their luminal membrane into a HCO3--rich (125 mM) luminal fluid against a sixfold concentration gradient. Since HCO3- transport cannot be achieved by luminal Cl-/HCO3- exchange under these conditions, we have investigated the possibility that it is mediated by an anion conductance. To determine whether the electrochemical potential gradient across the luminal membrane would favor HCO3- efflux, we have measured the intracellular potential (Vm) in microperfused, interlobular duct segments under various physiological conditions. When the lumen was perfused with a 124 mM Cl--25 mM HCO3- solution, a condition similar to the basal state, the resting potential was approximately -60 mV. Stimulation with dbcAMP or secretin caused a transient hyperpolarization (
5 mV) due to activation of electrogenic Na+-HCO3- cotransport at the basolateral membrane. This was followed by depolarization to a steady-state value of approximately -50 mV as a result of anion efflux across the luminal membrane. Raising the luminal HCO3- concentration to 125 mM caused a hyperpolarization (10 mV) in both stimulated and unstimulated ducts. These results can be explained by a model in which the depolarizing effect of Cl- efflux across the luminal membrane is minimized by the depletion of intracellular Cl- and offset by the hyperpolarizing effects of Na+-HCO3- cotransport at the basolateral membrane. The net effect is a luminally directed electrochemical potential gradient for HCO3- that is sustained during maximal stimulation. Our calculations indicate that the electrodiffusive efflux of HCO3- to the lumen via CFTR, driven by this gradient, would be sufficient to fully account for the observed secretory flux of HCO3-.
Key Words: pancreatic ducts • membrane potentials • bicarbonate ion • cystic fibrosis transmembrane conductance regulator • sodium-bicarbonate cotransporter
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