Acid secretion and proton conductance in human airway epithelium.
Acid secretion and proton conductive pathways across primary human airway surface epithelial cultures were investigated with the pH stat method in Ussing chambers and by single cell patch clamping. Cultures showed a basal proton secretion of 0.17 +/- 0.04 micromol.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 and 0.24 +/- 0.09 micromol.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 ZnCl(2) and was unaffected by mucosal bafilomycin A(1), Sch-28080, 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 pH 5.3-to-pH 7.3 gradient). We suggest that inflammatory processes activate proton secretion by the airway epithelium and acidify the airway surface liquid.
Fischer
Horst
H
Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, USA. hfischer@chori.org
Widdicombe
Jonathan H
JH
Illek
Beate
B
D000143:Acids / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D015194:Diffusion Chambers, Culture; D004232:Diuretics / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006632:Histamine / Q000493:pharmacokinetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000494:pharmacology; D008407:Mast Cells / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D011522:Protons; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D014132:Trachea / Q000166:cytology; D017967:Zinc Compounds / Q000494:pharmacology
D000143:Acids; D002712:Chlorides; D004232:Diuretics; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011522:Protons; D017967:Zinc Compounds; C035235:Sch 28080; D000584:Amiloride; D006632:Histamine; C016837:zinc chloride; D000255:Adenosine Triphosphate