Referenced in: none

Automatically associated channels: Kir2.3

Title: Chloride transport in nasal ciliated cells of cystic fibrosis heterozygotes.

Authors: Isabelle Sermet-Gaudelus, Michèle Déchaux, Benoit Vallée, Anne Fajac, Emanuelle Girodon, Thao Nguyen-Khoa, Rémi Marianovski, Ilse Hurbain, Jean Louis Bresson, Gérard Lenoir, Aleksander Edelman

Journal, date & volume: Am. J. Respir. Crit. Care Med., 2005 May 1 , 171, 1026-31

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15709055

Abstract
Studying subjects heterozygous for mutations of the cystic fibrosis (CF) gene may help clarify the impact on disease onset of CF transmembrane conductance regulator protein (CFTR-)-dependent chloride secretion. CFTR-mediated chloride transport was evaluated in 52 heterozygous subjects, 32 healthy control subjects, and 77 patients with CF with class I or II mutations. We measured the change in nasal potential difference in response to chloride-free isoproterenol solution for each subject and used a video-imaging fluorescent dye assay to assess the percentage of nasal ciliated cells with cAMP-dependent anion conductance. Our findings did not confirm the standard assumption that heterozygosity implies 50% of normal CFTR function. Half the heterozygous subjects had CFTR-mediated chloride transport levels below 50% of the normal range, and one-third had levels similar to those of the patients with CF. This reduced CFTR function was not associated with an elevated prevalence of CF-like symptoms in heterozygous subjects but was highly related to respiratory status in the patients with CF. These data suggest that CFTR-dependent chloride conductance does not directly modulate disease severity but may be part of a more global defect in patients with CF involving other CFTR functions or currently unknown modulatory factors.