The cystic fibrosis transmembrane conductance regulator (CFTR) inhibits ENaC through an increase in the intracellular Cl- concentration

被引:80
作者
König, J
Schreiber, R
Voelcker, T
Mall, M
Kunzelmann, K [1 ]
机构
[1] Univ Queensland, Dept Physiol & Pharmacol, Sch Biomed Sci, St Lucia, Qld 4072, Australia
[2] Univ Freiburg, Kinderklin, D-79106 Freiburg, Germany
关键词
D O I
10.1093/embo-reports/kve232
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Activation of the CFTR Cl- channel inhibits epithelial Na+ channels (ENaC), according to studies on epithelial cells and overexpressing recombinant cells. Here we demonstrate that ENaC is inhibited during stimulation of the cystic fibrosis trans-membrane conductance regulator (CFTR) in Xenopus oocytes, independent of the experimental set-up and the magnitude of the whole-cell current. Inhibition of ENaC is augmented at higher CFTR Cl- currents. Similar to CFTR, ClC-0 Cl- currents also inhibit ENaC, as well as high extracellular Na+ and Cl- in partially permeabilized oocytes. Thus, inhibition of ENaC is not specific to CFTR and seems to be mediated by Cl-.
引用
收藏
页码:1047 / 1051
页数:5
相关论文
共 23 条
[11]   CFTR-mediated inhibition of epithelial Na+ conductance in human colon is defective in cystic fibrosis [J].
Mall, M ;
Bleich, M ;
Kuehr, J ;
Brandis, M ;
Greger, R ;
Kunzelmann, K .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 1999, 277 (03) :G709-G716
[12]   Wild type but not Delta F508 CFTR inhibits Na+ conductance when coexpressed in Xenopus oocytes [J].
Mall, M ;
Hipper, A ;
Greger, R ;
Kunzelmann, K .
FEBS LETTERS, 1996, 381 (1-2) :47-52
[13]   Defective cholinergic Cl- secretion and detection of K+ secretion in rectal biopsies from cystic fibrosis patients [J].
Mall, M ;
Wissner, A ;
Seydewitz, HH ;
Kuehr, J ;
Brandis, M ;
Greger, R ;
Kunzelmann, K .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2000, 278 (04) :G617-G624
[14]   Inhibition of amiloride-sensitive epithelial Na+ absorption by extracellular nucleotides in human normal and cystic fibrosis airways [J].
Mall, M ;
Wissner, A ;
Gonska, T ;
Calenborn, D ;
Kuehr, J ;
Brandis, M ;
Kunzelmann, K .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2000, 23 (06) :755-761
[15]   The amiloride-inhibitable Na+ conductance is reduced by the cystic fibrosis transmembrane conductance regulator in normal but not in cystic fibrosis airways [J].
Mall, M ;
Bleich, M ;
Greger, R ;
Schreiber, R ;
Kunzelmann, K .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (01) :15-21
[16]   Non-specific activation of the epithelial sodium channel by the CFTR chloride channel [J].
Nagel, G ;
Szellas, T ;
Riordan, JR ;
Friedrich, T ;
Hartung, K .
EMBO REPORTS, 2001, 2 (03) :249-254
[17]   LOW ACCESS RESISTANCE PERFORATED PATCH RECORDINGS USING AMPHOTERICIN-B [J].
RAE, J ;
COOPER, K ;
GATES, P ;
WATSKY, M .
JOURNAL OF NEUROSCIENCE METHODS, 1991, 37 (01) :15-26
[18]   INTRACELLULAR CL ACTIVITY - EVIDENCE OF DUAL MECHANISMS OF CL ABSORPTION IN SWEAT-DUCT [J].
REDDY, MM ;
QUINTON, PM .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1994, 267 (04) :C1136-C1144
[19]   Activation of the epithelial Na+ channel (ENaC) requires CFTR Cl- channel function [J].
Reddy, MM ;
Light, MJ ;
Quinton, PM .
NATURE, 1999, 402 (6759) :301-304
[20]   The first-nucleotide binding domain of the cystic-fibrosis transmembrane conductance regulator is important for inhibition of the epithelial Na+ channel [J].
Schreiber, R ;
Hopf, A ;
Mall, M ;
Greger, R ;
Kunzelmann, K .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (09) :5310-5315