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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
Author(s) -
Briel M.,
Greger R.,
Kunzelmann K.
Publication year - 1998
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1998.825bp.x
Subject(s) - epithelial sodium channel , cystic fibrosis transmembrane conductance regulator , chemistry , transepithelial potential difference , sgk1 , cystic fibrosis , downregulation and upregulation , xenopus , amiloride , ionomycin , medicine , patch clamp , extracellular , ion transporter , endocrinology , intracellular , biochemistry , sodium , kinase , biology , membrane , receptor , organic chemistry , gene
1 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. 2 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. 3 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 ). 4 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. 5 Activation of endogenous Ca 2+ ‐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. 6 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.