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 (similar to 60 mu A/cm(2)) 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. Mel. Physiol. 16): L690-L698, 1997]. We have now measured isotopic fluxes of Cl-36(-) and Na-22(+) 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.