Cl− transport by cystic fibrosis transmembrane conductance regulator (CFTR) contributes to the inhibition of epithelial Na+ channels (ENaCs) in Xenopus oocytes co‐expressing CFTR and ENaC Journal Articles uri icon

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abstract

  • Epithelial Na+ channels (ENaCs) are inhibited by the cystic fibrosis transmembrane conductance regulator (CFTR) when CFTR is activated by protein kinase A. Since cAMP‐dependent activation of CFTR Cl− conductance is defective in cystic fibrosis (CF), ENaC currents are not inhibited by CFTR. This could explain the enhanced Na+ conductance found in CF. In the present study, we examined possible mechanisms of interaction between CFTR and ENaC co‐expressed in Xenopus oocytes. The magnitude of CFTR Cl− currents activated by 3‐isobutyl‐1‐methylxanthine (IBMX) in oocytes co‐expressing either wild‐type or mutant CFTR and ENaC determined the degree of downregulation of ENaC currents. The ability of CFTR to inhibit ENaC currents was significantly reduced either when extracellular Cl− was replaced by poorly conductive anions, e.g. SCN− or gluconate, or when CFTR was inhibited by diphenylamine‐carboxylate (DPC, 1 mmol l−1). Downregulation of ENaC was more pronounced at positive when compared with negative clamp voltages. This suggests that outward currents, i.e. influx of Cl− through activated CFTR most effectively downregulated ENaC. Activation of endogenous Ca2+‐activated Cl− currents by 1 μmol l−1 ionomycin did not inhibit ENaC current. This suggests that inhibition of ENaC mediated by Cl− currents may be specific to CFTR. The present findings indicate that downregulation of ENaC by CFTR is correlated to the ability of CFTR to conduct Cl−. The data have implications for how epithelia switch from NaCl absorption to NaCl secretion when CFTR is activated by secretagogues.

publication date

  • May 1998

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