General anesthetic octanol and related compounds activate wild-type and delF508 cystic fibrosis chloride channels

Br J Pharmacol. 2004 Mar;141(6):905-14. doi: 10.1038/sj.bjp.0705684. Epub 2004 Feb 16.


1. Cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel is defective during cystic fibrosis (CF). Activators of the CFTR Cl(-) channel may be useful for therapy of CF. Here, we demonstrate that a range of general anesthetics like normal-alkanols (n-alkanols) and related compounds can stimulate the Cl(-) channel activity of wild-type CFTR and delF508-CFTR mutant. 2. The effects of n-alkanols like octanol on CFTR activity were measured by iodide ((125)I) efflux and patch-clamp techniques on three distinct cellular models: (1). CFTR-expressing Chinese hamster ovary cells, (2). human airway Calu-3 epithelial cells and (3). human airway JME/CF15 epithelial cells which express the delF508-CFTR mutant. 3. Our data show for the first time that n-alkanols activate both wild-type CFTR and delF508-CFTR mutant. Octanol stimulated (125)I efflux in a dose-dependent manner in CFTR-expressing cells (wild-type and delF508) but not in cell lines lacking CFTR. (125)I efflux and Cl(-) currents induced by octanol were blocked by glibenclamide but insensitive to 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, as expected for a CFTR Cl(-) current. 4. CFTR activation by octanol was neither due to cell-to-cell uncoupling properties of octanol nor to an intracellular cAMP increase. CFTR activation by octanol requires phosphorylation by protein kinase-A (PKA) since it was prevented by H-89, a PKA inhibitor. 5. n-Alkanols chain length was an important determinant for channel activation, with rank order of potencies: 1-heptanol<1-octanol<2-octanol<1-decanol. Our findings may be of valuable interest for developing novel therapeutic strategies for CF.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells / drug effects
  • Calcium / analysis
  • Calcium / metabolism
  • Cell Line / drug effects
  • Chloride Channels / physiology*
  • Cricetinae
  • Cyclic AMP / analysis
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cystic Fibrosis
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Epithelial Cells
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Octanols / pharmacology*
  • Patch-Clamp Techniques


  • CFTR protein, human
  • Chloride Channels
  • Octanols
  • cystic fibrosis transmembrane conductance regulator delta F508
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Calcium