cAMP-dependent absorption of chloride across airway epithelium

Elevated levels of Na and Cl in airway surface liquid may play a major role in the airway pathology of cystic fibrosis (CF) (J. J. Smith, S. M. Travis , E. P. Greenberg, and M. J. Welsh. Cell 85: 229-236, 1996) and could be ca used by block of transcellular Cl absorption due to lack of a functional CF transmembrane conductance regulator(CFTR). To test for transcellular absor ption of CI across non-CF epithelium, we studied how fluid absorption was a ffected by the opening and closing of Cl channels. Forskolin tan activator of CFTR) tripled fluid absorption across primary cultures of bovine trachea l epithelium but had no effect on human cells. However, in both species, fl uid absorption was markedly inhibited by 5-nitra-2-(3-phenylpropylamino)ben zoate, a blocker of CPR. Microelectrode studies suggested that the magnitud e of the absorptive response to forskolin in bovine cells depended on the s ize of an inwardly directed electrochemical driving force for Cl movement a cross the apical membrane. Patch-clamp measurements of bovine cells reveale d CFTR in the apical membrane and a cAMP-activated, inwardly rectifying Cl channel in the basolateral membrane. We conclude that a significant fractio n of absorbed Cl passes transcellularly in bovine tracheal epithelial cultu res, with CFTR as the path of entry in the apical membrane and a novel cAMP -activated Cl channel as the exit route in the basolateral membrane. Our da ta further indicate that a similar pathway may exist in non-CF human trache al epithelium.