Wild type but not Delta F508 CFTR inhibits Na+ conductance when coexpressed in Xenopus oocytes

Airway epithelial cells bearing mutations of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) possess an increased Na+ conductance along with their well described defect of cAMP dependent Cl- conductance. Currently it is not clear, holy this occurs, and whether it is due to a CFTR control of epithelial Na+ conductances which might be defective in CF patients, In the present study, we have tried to identify possible interactions between both CFTR and the epithelial Na+ conductance by overexpressing respective cRNAs in Xenopus oocytes, The expression of all three (alpha, beta, gamma) subunits of the rat epithelial Na+ channel (rENaC) and wild type (wt) CFTR resulted in the expected amiloride sensitive Na+ and IBMX (1 mmol/l) activated Cl- currents, respectively, The amiloride sensitive Na+ conductance was, however, inhibited when the wt-CFTR Cl- conductance was activated by phosphodiesterase inhibition (IBMX), In contrast, IBMX had no such effect in Delta F508 and Na+ channels coexpressing oocytes, These results suggest that wt-CFTR, but not Delta F508-CFTR, is a cAMP dependent downregulator of epithelial Na+ channels. This may explain the higher Na+ conductance observed in airway epithelial cells of CF patients.