cAMP-dependent activation of CFTR inhibits the epithelial sodium channel (ENaC) without affecting its surface expression.
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.
Konstas
Angelos-Aristeidis
AA
University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK.
Koch
Jan-Peter
JP
Korbmacher
Christoph
C
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
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