Electrogenic bicarbonate secretion by guinea pig gallbladder epithelium: apical membrane exit
Stewart, C.P.; Winterhager, J.M.; Heintze, K.; Petersen, K.U.
American Journal of Physiology 256(4 Pt 1): C736-C749
1989
ISSN/ISBN: 0002-9513 PMID: 2468287 Document Number: 334989
Guinea pig gallbladder epithlium secretes HCO3- by electroneutral mechanisms, resulting in transeptihelial Cl--HCO3- exchange. Adenosine 3',5'-cyclic monophosphate (cAMP) converts HCO3- secretion into an electrogenic process. This transformation was examined using voltage-clamp, pH-stat, and microelectrode techniques. Prostaglandin E1 (PGE1;10-6M) was used to raise intracellular cAMP levels. It increased short-circuit current (Isc) by .apprx. 1.8 .mu.mol .cntdot. cm-2 .cntdot. h-1, an effect dependent on serosal HCO3 and, partly, on mucosal Cl-. Mucosal 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS; 10-3 M) halved Isc, but only in Cl--containing solutions. PGE1 increased the secretory HCO3- flux from .apprx. 2.0 to .apprx. 2.7 .mu.mol .cntdot. cm-2 .cntdot. h-1 and reduced the absorptive HCO3- flux from .apprx. 1.1 to .apprx. 0.5 .mu.mol .cntdot. cm-2 .cntdot. h-1, wiht net HCO3- secretion accounting for the increase in Isc. During single-cell impalements, PGE1 depolarized the apical membrane by > 10 mV (transiently in the absence of HCO3-) and decreased the apparent ratio of membrane resistance (Ra/Rb) from 5-8 to a value close to zero. These effects were largely reduced in magnitude and rapidity be removing Cl- and HCO3- from both sides of the epithelium. Ion substitutions in the luminal perfusate revealed substantial Cl- and HCO3- permeabilities at the apical membranes under PGE1 conditions. Our results indicate that, in the presence of PGE1 (cAMP), HCO3- crosses the apical membrane by two different routes. A SITS-sensitive fraction leaves the cell in eexhcange for luminal Cl-, which, in turn, recycles nto the lumen by electrodiffusion . The remaining HCO3- exits through a HCO3-conductive pathway.