Acid-base regulation of ion transport in rabbit ileum in vitro

Changes in acid-base balance have a major influence on ion transport in the ileum. The goals of the present study were to delineate (a) the specific transport processes most affected by changes in acid-base metabolism, (b) the individual roles of pH, PCO2, and concentration of HCO3- in modulating ion transport, and (c) the relationship between acid-base sensitive and other ion-transport systems. Ion transport and electrical parameters were measured in rabbit ilea in vitro under short-circuit conditions with systematic variations of pH, PCO2, and concentrations of HCO3-. Increasing HCO3- concentrations, with constant PCO2 and increasing pH, caused a decrease in electroneutral Na+ and Cl- absorption. At 5 mmol/L HCO3-, net fluxes of Na+ and Cl- were 5.9 +/- 1.4 and 4.5 +/- 1.1 microEq.cm-2.h-1, while at 50 mmol/L HCO3-, net Na+ and Cl- fluxes were 0.7 +/- 0.7 and 0.2 +/- 0.6 microEq.cm-2.h-1. Transepithelial HCO3(-)-gradient experiments suggested that serosal HCO3- was the principal factor. Changes in PCO2 showed a complex biphasic response, increasing net Cl- flux as PCO2 increased from 11-30 mm Hg in 5 mmol/L HCO3-; net Na+ flux increased as PCO2 was changed from 36 to greater than 100 mm Hg in 22 mmol/L HCO3-. In contrast, increasing pH in a bicarbonate-free N-2-hydroxyethylpiperazine-N'-2 = ethane sulfonic acid buffer did not significantly alter Na+ transport. Acid-base stimulated Na+ absorption was inhibited by 10(-3) mol/L amiloride, but not by bumetanide, consistent with the involvement of Na(+)-H+ exchange rather than Na(+)-Cl- cotransport. Epinephrine did not increase Na+ absorption under acid-base stimulated conditions, but glucose did, suggesting that the rate-limiting step for electroneutral absorptive processes under these conditions occurs at the apical rather than the basolateral membrane. Combining all experiments, a significant correlation existed between net flux of Na+ and HCO3- concentration (r = -0.72, P less than 0.05) and between net flux of Na+ and pH (r = -0.68, P less than 0.01). Chloride absorption was correlated with pH (r = 0.72, P less than 0.01). These results suggest a profound regulatory role for acid-base balance in electroneutral Na(+)-Cl- transport in rabbit ileum in vitro.