Disruption of monolayer integrity enables activation of a cystic fibrosis “bypass” channel in human

Abstract

Cystic fibrosis (CF) is a genetic disease characterized by marked reduction in Cl− conductance across many epithelia. Two kinds of Cl− channels have been associated with CF. One channel, termed the cystic fibrosis transmembrane conductance regulator (CFTR), is directly coded by the CF gene1–3. The other channel is an outwardly rectifying depolarization induced Cl− channel (ORDIC) that is distinguished from other outwardly rectifying chloride channels (ORCCs) because its activity is induced most reliably by patch excision and depolarization4–7. An issue in current CF research is whether ORDIC channels are indirectly activated by CFTR to contribute a significant portion of apical membrane Cl− conductance in airway cells6. We now show that ORDIC channels are readily activated in patches excised and depolarized from isolated cells, but are rarer or refractory to activation in patches from the apical membranes of confluent human airway epithelia. These findings have important implications for proposed therapies that would bypass the CFTR conductance by activating ORDIC channels.

Cite this article

Xia, Y., Haws, C. & Wine, J. Disruption of monolayer integrity enables activation of a cystic fibrosis “bypass” channel in human airway epithelia. Nat Med 3, 802–805 (1997). https://doi.org/10.1038/nm0797-802

View full text

>> Full Text:   Disruption of monolayer integrity enables activation of a cystic fibrosis “bypass” channel in human