Evidence that Calu-3 human airway cells secrete bicarbonate

The Calu-3 cell line is being investigated as a model for human submucosal gland serous cells. In a previous investigation of basal short- circuit current (I(sc)) in Calu-3 cells, high levels of bumetanide- insensitive basal I(sc) (~60 μA/cm²) were measured in cells grown at an air interface. Basal I(sc) was reduced only 7% by bumetanide, and the largest component of basal I(sc) required both Cl^- and HCO₃/^- in the bathing solutions. Because I(sc) could be partially inhibited by basolateral 4,4'- dinitrostilbene-2,2'-disulfonic acid and because the only known apical exit pathway for anions is the cystic fibrosis transmembrane conductance regulator, which has a relatively poor conductance for HCO₃/^-, it was concluded that most basal I(sc) is HCO₃/^- dependent Cl^- secretion [M. Singh, M. Krouse, S. Moon, and J. J. Wine. Am. J. Physiol. 272 (Lung Cell. Mol. Physiol. 16): L690-L698, 1997]. We have now measured isotopic fluxes of ³⁶Cl^- and ²²Na⁺ across short-circuited Calu-3 cells and found that virtually none of the basal I(sc) is Cl^- secretion or Na⁺ absorption. Thus, in contrast to the earlier report, we conclude that the major component of basal I(sc) is HCO₃/^- secretion. Stimulation recruits primarily Cl^- secretion, as previously proposed.