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Articles in PresS, published online ahead of print November 13, 2001
Am J Physiol Cell Physiol, 10.1152/ajpcell.00369.2001
Submitted on August 2, 2001
Accepted on November 8, 2001
1 Children's Hospital Oakland Research Institute, Oakland, CA, USA
* To whom correspondence should be addressed. E-mail: hfischer{at}chori.org.
Acid secretion and proton conductive pathways across primary human airway surface epithelial cultures were investigated using the pH stat method in Ussing chambers and by single cell patch clamping. Cultures showed a basal proton secretion of 0.17 ± 0.04 µmole*h-1*cm-2 and mucosal pH equilibrated at 6.85 ± 0.26. Addition of histamine or ATP to the mucosal medium increased proton secretion by 0.27 ± 0.09 µmole*h-1*cm-2 and 0.24 ± 0.09 µmole*h-1*cm-2 , respectively. Addition of mast cells to the mucosal medium of airway cultures similarly activated proton secretion. Stimulated proton secretion was similar in cultures bathed mucosally with either NaCl Ringer or ion-free mannitol solutions. Proton secretion was potently blocked by mucosal ZnCl2 and was unaffected by mucosal bafilomycin A1, Sch28080 or ouabain. Mucosal amiloride blocked proton secretion in tissues that showed large amiloride-sensitive potentials. Proton secretion was sensitive to the application of transepithelial current and showed outward rectification. In whole cell patch clamp recordings a strongly outward-rectifying, zinc-sensitive, depolarization-activated proton conductance was identified with an average chord conductance of 9.2 ± 3.8 pS/pF (at 0 mV and a pH5.3-to-pH7.3 gradient). We suggest that inflammatory processes activate proton secretion by the airway epithelium and acidify the airway surface liquid.
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