Amiloride‐sensitive fluid resorption in NCI‐H441 lung epithelia depends on an apical Cl− conductance. Issue 1 (16th January 2014)

• Record Type: Journal Article
• Authors: Korbmacher, Jonas P.; Michel, Christiane; Neubauer, Daniel; Thompson, Kristin; Mizaikoff, Boris; Frick, Manfred; Dietl, Paul; Wittekindt, Oliver H.
• Is Part Of: Physiological reports. Volume 2:Issue 1(2014:Jan.)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2014-01-16
• Subjects: Physiology -- Periodicals; 571
• DOI: 10.1002/phy2.201
• Languages: English
• ISSNs: 2051-817X

Abstract

<abstract abstract-type="main" id="phy2201-abs-0001"> <title>Abstract</title> <p>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 (<italic>I</italic><sub>SC</sub>) measurements with a novel D<sub>2</sub>O dilution method to correlate ion and water transport in order to reveal basic transport mechanisms in lung epithelia. D<sub>2</sub>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 <italic>μ</italic>L/(h cm<sup>2</sup>). Water resorption and <italic>I</italic><sub>SC</sub> were reduced by almost 80% in the presence of the bulk Cl<sup>−</sup> channel inhibitor 5‐nitro‐2‐(3‐phenylpropylamino)benzoic acid (NPPB) or amiloride, a specific inhibitor of epithelial sodium channel (ENaC). However, water resorption and <italic>I</italic><sub>SC</sub> were only moderately affected by forskolin or cystic fibrosis transmembrane regulator (CFTR) channel inhibitors (CFTR<sub>inh</sub>‐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<sup>−</sup> conductance.</p> </abstract>