Basal chloride currents in murine airway epithelial cells: modulation by CFTR.
We have isolated ciliated respiratory cells from the nasal epithelium of wild-type and cystic fibrosis (CF) null mice and used the patch-clamp technique to investigate their basal conductances. Current-clamp experiments on unstimulated cells indicated the presence of K+ and Cl- conductances and, under certain conditions, a small Na+ conductance. Voltage-clamp experiments revealed three distinct Cl- conductances. Itv-indep was time and voltage independent with a linear current-voltage (I-V) plot; Iv-act exhibited activation at potentials greater than +/- 50 mV, giving an S-shaped I-V plot; and Ihyp-act was activated by hyperpolarizing potentials and had an inwardly rectified I-V plot. The current density sequence was Ihyp-act = Iv-act >> Itv-indep. These conductances had Cl(-)-to-N-methyl-D-glucamine cation permeability ratios of between 2.8 and 10.3 and were unaffected by tamoxifen, flufenamate, glibenclamide, DIDS, and 5-nitro-2-(3-phenylpropylamino) benzoic acid but were inhibited by Zn2+ and Gd3+. Itv-indep and Iv-act were present in wild-type and CF cells at equal density and frequency. However, Ihyp-act was detected in only 3% of CF cells compared with 26% of wild-type cells, suggesting that this conductance may be modulated by cystic fibrosis transmembrane conductance regulator (CFTR).
Tarran
R
R
Department of Physiological Sciences, University Medical School, Newcastle upon Tyne, United Kingdom.
Gray
M A
MA
Evans
M J
MJ
Colledge
W H
WH
Ratcliff
R
R
Argent
B E
BE
D000818:Animals; D000838:Anions / Q000378:metabolism; D002712:Chlorides / Q000502:physiology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology*; D004553:Electric Conductivity; D004847:Epithelial Cells / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009297:Nasal Mucosa / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques
D000838:Anions; D002712:Chlorides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator