CFTR-mediated anion conductance regulates Na+-K+-pump activity in Calu-3 human airway cells

We studied the role of CFTR in the Na+-K+-pump activity of Calu-3 human airway cells. To estimate the Na+-K+-pump activity on the basolateral membrane, the ouabain-sensitive component of the short-circuit current (Isc) was measured after permeabilization of the apical membrane with nystatin, a Na+ ionophore. The Na+-K+-pump activity was diminished by a selective CFTR blocker (glybenclamide) or nonspecific Cl- channel inhibitors (NPPB and DPC) but not by outwardly rectifying Cl- channel blockers (DNDS, DIDS). Augmentation of anion conductance by 8-bromo-cyclic AMP (8Br-cAMP, 1 mM) potentiated the Na+-K+-pump activity that was reduced by blocking CFTR or by the replacement of Cl- with gluconate, a less membrane-permeant anion. The Na+-K+-pump activity was unaffected by the replacement of Cl- with NO, that has equal permeability through the CFTR. These results suggest that the anion movement through the CFTR may contribute to the Na+-K+-pump activity in Calu-3 cells by regulating the rate of Na+ entry. (C) 2000 Academic Press.