Mechanism of sodium hyperabsorption in cultured cystic fibrosis nasal epithelium: a patch-clamp study.
Transepithelial Na+ absorption is increased two to three times in cystic fibrosis (CF) compared with normal (NL) airway epithelia. This increase has been associated with a higher Na+ permeability of the apical membrane of airway epithelial cells. Because Na+ absorption is electrogenic and abolished by amiloride, Na+ channels are thought to dominate the apical membrane Na+ permeability. Three Na+ channel-related mechanisms may explain the increase in apical Na+ permeability in CF cells: increased number of channels, increased single-channel conductance, and increased single-channel open probability. We compared the properties of Na(+)-permeable channels in the apical membrane of confluent preparations of human NL and CF nasal epithelial cells cultured on permeable supports. Na(+)-permeable channels were studied using the patch-clamp technique in the excised inside-out and cell-attached configurations. The same types of Na(+)-permeable channels were recorded in CF and NL cells. In excised patches, nonselective (Na+/K+) cation channels were recorded, and no differences between CF and NL were found in the properties, incidence, single-channel conductance, and single-channel open probability. In cell-attached patches, channels with a higher Na+ vs. K+ selectivity dominated. There was no difference between CF and NL cells in the incidence (18.8 vs. 21.4%, respectively) and conductance (17.2 +/- 2.8 vs. 21.4 +/- 1.5 pS, respectively) of Na(+)-permeable channels. However, the open probability was higher in CF cells compared with NL cells (30.0 +/- 3.4%, n = 6, vs. 15.0 +/- 3.9%, n = 13; P < 0.05). We conclude that, in CF nasal epithelial cells, the increase in Na+ permeability of the apical membrane results from an increase in the open probability of Na(+)-permeable channels in the apical membrane.
Chinet
T C
TC
University of North Carolina, School of Medicine, Chapel Hill 27599-7020.
Fullton
J M
JM
Yankaskas
J R
JR
Boucher
R C
RC
Stutts
M J
MJ
D000042:Absorption; D002412:Cations / Q000378:metabolism; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004594:Electrophysiology; D006801:Humans; D007473:Ion Channels / Q000378:metabolism / Q000502:physiology; D009297:Nasal Mucosa / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010539:Permeability; D012016:Reference Values; D012964:Sodium / Q000493:pharmacokinetics*
D002412:Cations; D007473:Ion Channels; D012964:Sodium