title: cAMP-dependent activation of CFTR inhibits the epithelial sodium channel (ENaC) without affecting its surface expression.
abstract: The cystic fibrosis transmembrane conductance regulator (CFTR) is thought to modulate epithelial sodium channel (ENaC) function in various preparations. However, the molecular nature and (patho-)physiological significance of the CFTR/ENaC interaction is still unclear and may vary in different tissues. Co-expression experiments in Xenopus laevis oocytes are a popular approach to investigate a possible functional interaction of CFTR and ENaC but have revealed controversial results. We could confirm previous reports that in oocytes co-expressing ENaC and CFTR the amiloride-sensitive current was reduced during cAMP-mediated stimulation of CFTR. In contrast, co-expression of CFTR per se had no effect on baseline ENaC currents. ENaC with Liddle's syndrome mutation is also inhibited during activation of CFTR, suggesting that the C-terminus of the ENaC beta-subunit is not important for this functional interrelation. Single-channel patch-clamp recordings demonstrated that co-expression of CFTR does not alter the single-channel conductance of ENaC. Using a chemiluminescence assay we demonstrated that the inhibition of ENaC during cAMP-dependent activation of CFTR was not associated with a decrease in ENaC surface expression. We conclude that the inhibitory effect of cAMP-activated CFTR on ENaC is due to a decrease in channel open probability.
authors.affiliation: University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK.
authors.forename: Angelos-Aristeidis
authors.initials: AA
authors.lastname: Konstas
authors.forename: Jan-Peter
authors.initials: JP
authors.lastname: Koch
authors.forename: Christoph
authors.initials: C
authors.lastname: Korbmacher
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D053503:Epithelial Sodium Channels; D015870:Gene Expression; D006801:Humans; D006929:Hyperaldosteronism / Q000235:genetics / Q000378:metabolism; D015640:Ion Channel Gating / Q000502:physiology; D008163:Luminescent Measurements; D008565:Membrane Proteins / Q000378:metabolism; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D051381:Rats; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: C505032:CFTR protein, human; D053503:Epithelial Sodium Channels; D008565:Membrane Proteins; C507048:SCNN1B protein, human; C507050:Scnn1b protein, rat; D015222:Sodium Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP; D011188:Potassium