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Am J Physiol Cell Physiol 274: C904-C913, 1998;
0363-6143/98 $5.00
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Vol. 274, Issue 4, C904-C913, April 1998

Basal chloride currents in murine airway epithelial cells: modulation by CFTR

R. Tarran1, M. A. Gray1, M. J. Evans2, W. H. Colledge2, R. Ratcliff2, and B. E. Argent1

1 Department of Physiological Sciences, University Medical School, Newcastle upon Tyne NE2 4HH; and 2 Wellcome/Cancer Research Campaign Institute of Cancer and Developmental Biology, Cambridge CB2 1QR, United Kingdom

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).

nasal epithelial cells; chloride conductance; patch-clamp technique; cystic fibrosis; transgenic mice; cystic fibrosis transmembrane conductance regulator


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