273 237

Cited 290 times in

Aberrant CFTR-dependent HCO3- transport in mutations associated with cystic fibrosis

Authors
 Joo Young Choi  ;  Daniella Muallem  ;  Kirill Kiselyov  ;  Min Goo Lee  ;  Philip J. Thomas  ;  Shmuel Muallem 
Citation
 NATURE, Vol.410(6824) : 94-97, 2001 
Journal Title
 NATURE 
ISSN
 0028-0836 
Issue Date
2001
MeSH
Bicarbonates/metabolism* ; Biological Transport ; Cell Line ; Chlorides/metabolism ; Cystic Fibrosis/metabolism* ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism* ; Humans ; Membrane Potentials ; Membranes/metabolism ; Mutagenesis, Site-Directed ; Mutation ; Pancreas/metabolism ; Transfection
Abstract
Cystic fibrosis (CF) is a disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). Initially, Cl- conductance in the sweat duct was discovered to be impaired in CF, a finding that has been extended to all CFTR-expressing cells. Subsequent cloning of the gene showed that CFTR functions as a cyclic-AMP-regulated Cl- channel; and some CF-causing mutations inhibit CFTR Cl- channel activity. The identification of additional CF-causing mutants with normal Cl- channel activity indicates, however, that other CFTR-dependent processes contribute to the disease. Indeed, CFTR regulates other transporters, including Cl(-)-coupled HCO3- transport. Alkaline fluids are secreted by normal tissues, whereas acidic fluids are secreted by mutant CFTR-expressing tissues, indicating the importance of this activity. HCO3- and pH affect mucin viscosity and bacterial binding. We have examined Cl(-)-coupled HCO3- transport by CFTR mutants that retain substantial or normal Cl- channel activity. Here we show that mutants reported to be associated with CF with pancreatic insufficiency do not support HCO3- transport, and those associated with pancreatic sufficiency show reduced HCO3- transport. Our findings demonstrate the importance of HCO3- transport in the function of secretory epithelia and in CF.
Files in This Item:
T200103238.pdf Download
DOI
10.1038/35065099
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/142888
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse