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

We have isolatedciliated respiratory cells from the nasal epithelium of wild-type andcystic fibrosis (CF) null mice and used the patch-clamp technique toinvestigate their basal conductances. Current-clamp experiments onunstimulated cells indicated the presence ofK⁺ andCl conductances and, undercertain conditions, a small Na⁺conductance. Voltage-clamp experiments revealed three distinct Cl conductances.I_tv-indep wastime and voltage independent with a linear current-voltage(I-V)plot; I_v-actexhibited activation at potentials greater than ±50 mV, giving anS-shapedI-Vplot; andI_hyp-act wasactivated by hyperpolarizing potentials and had an inwardly rectifiedI-Vplot. The current density sequence was I_hyp-act = I_v-act  I_tv-indep. Theseconductances hadCl-to-N-methyl-D-glucaminecation permeability ratios of between 2.8 and 10.3 and were unaffectedby tamoxifen, flufenamate, glibenclamide, DIDS, and5-nitro-2-(3-phenylpropylamino) benzoic acid but were inhibited byZn²⁺ andGd³⁺.I_tv-indep andI_v-act werepresent in wild-type and CF cells at equal density and frequency.However, I_hyp-actwas detected in only 3% of CF cells compared with 26% of wild-typecells, suggesting that this conductance may be modulated by cysticfibrosis transmembrane conductance regulator (CFTR).