Figure 1. Effect of anion substitution in the bathing medium on basal and cAMP-stimulated short-circuit current across wild-type murine duodenum. Transepithelial short-circuit current (Isc, an index of anion secretion) was measured in Ringers media containing both chloride and bicarbonate (Cl-+ HCO3-), only chloride (Cl-) or only bicarbonate (HCO3 -) as CFTR-permeant anions. Measurements were made during sequential periods: Basal, during cAMP stimulation by bilateral addition of 10 μM forskolin + 100 μM isobutyl methylxanthine (cAMP), and following addition of 100 μM bumetanide (an inhibitor of Clsecretion) to the serosal bath (Bumet). The data provide evidence that CFTR carries bicarbonate current during cAMP stimulation. First, a significant bumetanideinsensitive Isc is present only when HCO3 - is present in the bathing medium. Second, a significant cAMP current is stimulated when HCO3 - is the only permeant anion available for transport by CFTR. In contrast, these responses are minimal in CFTR knockout duodenum (data not shown). Letters indicate