CFTR-like chloride channels in non-ciliated bronchiolar epithelial (Clara) cells

TC Chinet, SE Gabriel, CM Penland, M Sato… - Biochemical and …, 1997 - Elsevier
TC Chinet, SE Gabriel, CM Penland, M Sato, MJ Stutts, RC Boucher, MR Van Scott
Biochemical and biophysical research communications, 1997Elsevier
Distal airways are believed to be a major site of disease in cystic fibrosis. The product of the
CF gene, CFTR, is expressed in non-ciliated bronchiolar epithelial (Clara) cells. Clara cells
in primary culture are capable of Cl− secretion which can be stimulated by cAMP and
extracellular nucleotides. We used the patch clamp technique to look for Cl− channels in the
apical membrane of rabbit Clara cells. In cell-attached patches, we recorded Cl− channels
with a conductance for outward currents of 7.5±0.4 pS (n= 10) and for inward currents of …
Distal airways are believed to be a major site of disease in cystic fibrosis. The product of the CF gene, CFTR, is expressed in non-ciliated bronchiolar epithelial (Clara) cells. Clara cells in primary culture are capable of Clsecretion which can be stimulated by cAMP and extracellular nucleotides. We used the patch clamp technique to look for Clchannels in the apical membrane of rabbit Clara cells. In cell-attached patches, we recorded Clchannels with a conductance for outward currents of 7.5 ± 0.4 pS (n = 10) and for inward currents of 3.2 ± 0.5 pS (n = 10); these channels typically exhibited slow kinetics and were not inhibited by the Clchannel blockers NPPB and DIDS. Channel activity was not noticeably dependent on pipette potential. Addition of chlorophenylthio-cyclic AMP (cpt-cAMP) to the bath increased the percentage of cell-attached patches with active channels (33.8% vs 56.7%; p< 0.05) and the channel open probability (0.49 ± 0.03 vs 0.84 ± 0.02; p< 0.05). Extracellular ATP increased the percentage of cell-attached patches with active channels (28.7% to 50.0%; p< 0.05) but had no significant effect on the channel open probability (0.62 ± 0.07 vs 0.60 ± 0.06). In conclusion, rabbit non-ciliated bronchiolar epithelial cells express low-conductance Clchannels that share many similarities with the CFTR-related Clchannel and are regulated by cAMP and extracellular ATP.
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