Figure 3. Effects of luminal Cl- removal and EIPA on bicarbonate secretion and Isc across CF murine duodenum. Replacing luminal Cl- content (3a) with the poorly permeable anion, isethionate, resulted in net acid secretion by CF duodenum that was abolished by subsequent cAMP stimulation using a forskolin/IBMX cocktail. The imposed cell-to-lumen and mucosal-toserosal chloride gradient resulted in high basal Isc in the CF duodenum. However, cAMP stimulation did not increase Isc under this condition (n = 13). To determine whether a change in proton secretion via a luminal membrane Na+/H+ exchanger was responsible for the change in Jsm HCO 3, the CF duodenum was treated with EIPA (3b), an inhibitor of intestinal Na+/H+ exchangers (NHE2 and NHE3). EIPA treatment resulted in a stable increase in the basal bicarbonate secretion and prevented cAMP stimulation of Jsm HCO 3. However, a significant increase in Isc was still apparent following forskolin/IBMX in the presence of EIPA (n = 8). * Significantly different from Basal.