Open AccessAmiloride‐sensitive fluid resorption in NCI ‐H441 lung epithelia depends on an apical Cl − conductance
Author(s) -
Korbmacher Jonas P.,
Michel Christiane,
Neubauer Daniel,
Thompson Kristin,
Mizaikoff Boris,
Frick Manfred,
Dietl Paul,
Wittekindt Oliver H.
Publication year - 2014
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.1002/phy2.201
Subject(s) - amiloride , resorption , apical membrane , chemistry , cystic fibrosis transmembrane conductance regulator , epithelial sodium channel , transepithelial potential difference , biophysics , medicine , water transport , endocrinology , ion transporter , sodium , cystic fibrosis , water flow , biochemistry , biology , membrane , organic chemistry , environmental engineering , engineering
Proper apical airway surface hydration is essential to maintain lung function. This hydration depends on well‐balanced water resorption and secretion. The mechanisms involved in resorption are still a matter of debate, especially as the measurement of transepithelial water transport remains challenging. In this study, we combined classical short circuit current ( I SC ) measurements with a novel D 2 O dilution method to correlate ion and water transport in order to reveal basic transport mechanisms in lung epithelia. D 2 O dilution method enabled precise analysis of water resorption with an unprecedented resolution. NCI ‐H441 cells cultured at an air–liquid interface resorbed water at a rate of 1.5 ± 0.4 μ L/(h cm 2 ). Water resorption and I SC were reduced by almost 80% in the presence of the bulk Cl − channel inhibitor 5‐nitro‐2‐(3‐phenylpropylamino)benzoic acid ( NPPB ) or amiloride, a specific inhibitor of epithelial sodium channel ( ENaC ). However, water resorption and I SC were only moderately affected by forskolin or cystic fibrosis transmembrane regulator ( CFTR ) channel inhibitors ( CFTR inh ‐172 and glybenclamide). In line with previous studies, we demonstrate that water resorption depends on ENaC , and CFTR channels have only a minor but probably modulating effect on water resorption. However, the major ENaC ‐mediated water resorption depends on an apical non‐ CFTR Cl − conductance.