Rauh R, Hörner C, Korbmacher C (2017)
Publication Type: Journal article
Publication year: 2017
Book Volume: 312
Pages Range: L277-L287
Journal Issue: 2
DOI: 10.1152/ajplung.00375.2016
The epithelial sodium channel (ENaC) and the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel critically regulate airway surface liquid by driving fluid absorption and secretion, respectively. Their functional interplay is complex and incompletely understood. ENaC is a heteromeric channel with three well-characterized subunits (?, ?, and ?). In humans, an additional ?-ENaC subunit exists in lung and several other tissues, where it may replace the ?-subunit to form ???-ENaC. Little is known about the physiological role of ???-ENaC and its possible interaction with CFTR. The aim of the present study was to investigate the effect of human CFTR on human ???-ENaC heterologously expressed in Xenopus laevis oocytes. In oocytes coexpressing ???-ENaC and CFTR the ENaC-mediated amiloride-sensitive whole cell current (?Iami) was reduced by ~50% compared with that measured in oocytes expressing ???-ENaC alone. Moreover, basal level of proteolytic ENaC activation was reduced in the presence of CFTR. The inhibitory effect of CFTR on ???-ENaC was due to a combination of decreased average open probability (Po) and reduced channel expression at the cell surface. Interestingly, in oocytes expressing ???-ENaC, increasing intracellular [cAMP] by IBMX and forskolin increased ?Iami by ~50%. This stimulatory effect was not observed for human and rat ???-ENaC and was independent of CFTR coexpression and coactivation. Experiments with a mutant channel (??S520C?-ENaC) which can be converted to a channel with a Po of nearly 1 suggested that cAMP activates ???-ENaC by increasing Po In conclusion, our results demonstrate that ???-ENaC is inhibited by CFTR but activated by cAMP.
APA:
Rauh, R., Hörner, C., & Korbmacher, C. (2017). δβγ-ENaC is inhibited by CFTR but stimulated by cAMP in Xenopus laevis oocytes. American Journal of Physiology-Lung Cellular and Molecular Physiology, 312(2), L277-L287. https://doi.org/10.1152/ajplung.00375.2016
MLA:
Rauh, Robert, Christian Hörner, and Christoph Korbmacher. "δβγ-ENaC is inhibited by CFTR but stimulated by cAMP in Xenopus laevis oocytes." American Journal of Physiology-Lung Cellular and Molecular Physiology 312.2 (2017): L277-L287.
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