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 (Isc) in Calu-3 cells, high levels of bumetanide-insensitive basal Isc (approximately 60 microA/cm2) were measured in cells grown at an air interface. Basal Isc was reduced only 7% by bumetanide, and the largest component of basal Isc required both Cl- and HCO3- in the bathing solutions. Because Isc 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 Isc 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 Isc is Cl- secretion or Na+ absorption. Thus, in contrast to the earlier report, we conclude that the major component of basal Isc is HCO3- secretion. Stimulation recruits primarily Cl- secretion, as previously proposed.