Epithelial Sodium Channels Regulate Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channels in XenopusOocytes

Qinshi Jiang; Jinqing Li; Rachael Dubroff; Yoon J. Ahn; J.Kevin Foskett; John Engelhardt; Thomas R. Kleyman

doi:10.1074/jbc.275.18.13266

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Epithelial Sodium Channels Regulate Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channels in XenopusOocytes

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Epithelial Sodium Channels Regulate Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channels in XenopusOocytes

Qinshi Jiang, Jinqing Li, Rachael Dubroff, Yoon J. Ahn, J.Kevin Foskett, John Engelhardt and Thomas R. Kleyman

The Journal of biological chemistry, Vol.275(18), pp.13266-13274

05/05/2000

DOI: 10.1074/jbc.275.18.13266

PMID: 10788432

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Abstract

The cystic fibrosis transmembrane conductance regulator (CFTR), in addition to its well defined Cl− channel properties, regulates other ion channels. CFTR inhibits epithelial Na+ channel (ENaC) currents in many epithelial and nonepithelial cells. Because modulation of net NaCl reabsorption has important implications in extracellular fluid volume homeostasis and airway fluid volume and composition, we investigated whether this regulation was reciprocal by examining whether ENaC regulates CFTR. Co-expression of human (h) CFTR and mouse (m) αβγENaC in Xenopus oocytes resulted in a significant, 3.7-fold increase in whole-cell hCFTR Cl−conductance compared with oocytes expressing hCFTR alone. The forskolin/3-isobutyl-1-methylxanthine-stimulated whole-cell conductance in hCFTR-mENaC co-injected oocytes was amiloride-insensitive, indicating an inhibition of mENaC following hCFTR activation, and it was blocked by DPC (diphenylamine-2-carboxylic acid) and was DIDS (4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid)-insensitive. Enhanced hCFTR Cl− conductance was also observed when either the α- or β-subunit of mENaC was co-expressed with hCFTR, but this was not seen when CFTR was co-expressed with the γ-subunit of mENaC. Single Cl− channel analyses showed that both CFTR Cl− channel open probability and the number of CFTR Cl− channels detected per patch increased when hCFTR was co-expressed with αβγmENaC. We conclude that in addition to acting as a regulator of ENaC, CFTR activity is regulated by ENaC.

Details

Title: Subtitle: Epithelial Sodium Channels Regulate Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channels in XenopusOocytes
Creators: Qinshi Jiang - University of Pennsylvania
Jinqing Li - University of Pennsylvania
Rachael Dubroff - University of Pennsylvania
Yoon J. Ahn - University of Pennsylvania
J.Kevin Foskett - University of Pennsylvania
John Engelhardt - University of Iowa
Thomas R. Kleyman - University of Pennsylvania
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.275(18), pp.13266-13274
DOI: 10.1074/jbc.275.18.13266
PMID: 10788432
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: Elsevier Inc
Language: English
Date published: 05/05/2000
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
Record Identifier: 9984284456202771

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