Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1993 Apr;91(4):1590–1597. doi: 10.1172/JCI116365

Fluid and electrolyte transport by cultured human airway epithelia.

J J Smith 1, M J Welsh 1
PMCID: PMC288135  PMID: 8473502

Abstract

An understanding of the fluid and electrolyte transport properties of any epithelium requires knowledge of the direction, rate, and regulation of fluid transport and the composition of the fluid. Although human airway epithelial likely play a key role in controlling the quantity and composition of the respiratory tract fluid, evidence for such a role is not available. To obtain such knowledge, we measured fluid and electrolyte transport by cultured human nasal epithelia. Under basal conditions we found that epithelia absorbed Na+ and fluid; both processes were inhibited by addition of amiloride to the mucosal surface. These data suggest that active Na+ absorption is responsible for fluid absorption. Interestingly, Na+ absorption was not accompanied by the net absorption of Cl-; some other anion accompanied Na+. The combination of cAMP agonists and mucosal amiloride stimulated the secretion of NaCl-rich fluid. But surprisingly, the response to cAMP agonists in the absence of amiloride showed substantial intersubject variability: cAMP stimulated fluid secretion across some epithelia, for others, cAMP stimulated fluid absorption. The explanation for the differences in response is uncertain, but we speculate that the magnitude of apical membrane Na+ conductance may modulate the direction of fluid transport in response to cAMP. We also found that airway epithelial secrete H+ and absorb K+ under basal conditions; both processes were inhibited by cAMP agonists. Because the H+/K(+)-ATPase inhibitor, SCH 28080, inhibited K+ absorption, an apical membrane H+/K(+)-ATPase may be at least partly responsible for K+ and H+ transport. However, H+/K+ exchange could not entirely account for the luminal acidification. The finding that cAMP agonists inhibited luminal acidification may be explained by the recent finding that cAMP increases apical HCO3- conductance. These results provide new insights into how the intact airway epithelium may modify the composition of the respiratory tract fluid.

Full text

PDF
1590

Images in this article

1592Image
on p.1592
1593Image
on p.1593

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adamson T. M., Boyd R. D., Platt H. S., Strang L. B. Composition of alveolar liquid in the foetal lamb. J Physiol. 1969 Sep;204(1):159–168. doi: 10.1113/jphysiol.1969.sp008905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Al-Bazzaz F. J., Al-Awqati Q. Interaction between sodium and chloride transport in canine tracheal mucosa. J Appl Physiol Respir Environ Exerc Physiol. 1979 Jan;46(1):111–119. doi: 10.1152/jappl.1979.46.1.111. [DOI] [PubMed] [Google Scholar]
  3. Al-Bazzaz F. J. Role of cyclic AMP in regulation of chloride secretion by canine tracheal mucosa. Am Rev Respir Dis. 1981 Mar;123(3):295–298. doi: 10.1164/arrd.1981.123.3.295. [DOI] [PubMed] [Google Scholar]
  4. App E. M., King M., Helfesrieder R., Köhler D., Matthys H. Acute and long-term amiloride inhalation in cystic fibrosis lung disease. A rational approach to cystic fibrosis therapy. Am Rev Respir Dis. 1990 Mar;141(3):605–612. doi: 10.1164/ajrccm/141.3.605. [DOI] [PubMed] [Google Scholar]
  5. Boat T. F., Cheng P. W. Biochemistry of airway mucus secretions. Fed Proc. 1980 Nov;39(13):3067–3074. [PubMed] [Google Scholar]
  6. Boucher R. C., Cotton C. U., Gatzy J. T., Knowles M. R., Yankaskas J. R. Evidence for reduced Cl- and increased Na+ permeability in cystic fibrosis human primary cell cultures. J Physiol. 1988 Nov;405:77–103. doi: 10.1113/jphysiol.1988.sp017322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Boucher R. C., Stutts M. J., Bromberg P. A., Gatzy J. T. Regional differences in airway surface liquid composition. J Appl Physiol Respir Environ Exerc Physiol. 1981 Mar;50(3):613–620. doi: 10.1152/jappl.1981.50.3.613. [DOI] [PubMed] [Google Scholar]
  8. Boucher R. C., Stutts M. J., Knowles M. R., Cantley L., Gatzy J. T. Na+ transport in cystic fibrosis respiratory epithelia. Abnormal basal rate and response to adenylate cyclase activation. J Clin Invest. 1986 Nov;78(5):1245–1252. doi: 10.1172/JCI112708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. CHERNICK W. S., BARBERO G. J. Composition of tracheobronchial secretions in cystic fibrosis of the pancreas and bronchiectasis. Pediatrics. 1959 Nov;24:739–745. [PubMed] [Google Scholar]
  10. Cheek J. M., Kim K. J., Crandall E. D. Tight monolayers of rat alveolar epithelial cells: bioelectric properties and active sodium transport. Am J Physiol. 1989 Mar;256(3 Pt 1):C688–C693. doi: 10.1152/ajpcell.1989.256.3.C688. [DOI] [PubMed] [Google Scholar]
  11. Coleman D. L., Tuet I. K., Widdicombe J. H. Electrical properties of dog tracheal epithelial cells grown in monolayer culture. Am J Physiol. 1984 Mar;246(3 Pt 1):C355–C359. doi: 10.1152/ajpcell.1984.246.3.C355. [DOI] [PubMed] [Google Scholar]
  12. Cott G. R., Sugahara K., Mason R. J. Stimulation of net active ion transport across alveolar type II cell monolayers. Am J Physiol. 1986 Feb;250(2 Pt 1):C222–C227. doi: 10.1152/ajpcell.1986.250.2.C222. [DOI] [PubMed] [Google Scholar]
  13. Cotton C. U., Stutts M. J., Knowles M. R., Gatzy J. T., Boucher R. C. Abnormal apical cell membrane in cystic fibrosis respiratory epithelium. An in vitro electrophysiologic analysis. J Clin Invest. 1987 Jan;79(1):80–85. doi: 10.1172/JCI112812. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Cullen J. J., Welsh M. J. Regulation of sodium absorption by canine tracheal epithelium. J Clin Invest. 1987 Jan;79(1):73–79. doi: 10.1172/JCI112811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Doucet A., Marsy S. Characterization of K-ATPase activity in distal nephron: stimulation by potassium depletion. Am J Physiol. 1987 Sep;253(3 Pt 2):F418–F423. doi: 10.1152/ajprenal.1987.253.3.F418. [DOI] [PubMed] [Google Scholar]
  16. Hersey S. J., Steiner L., Mendlein J., Rabon E., Sachs G. SCH28080 prevents omeprazole inhibition of the gastric H+/K+-ATPase. Biochim Biophys Acta. 1988 Aug 31;956(1):49–57. doi: 10.1016/0167-4838(88)90296-8. [DOI] [PubMed] [Google Scholar]
  17. Johnsen A. H., Nielsen R. Enhanced sensitivity to stimulation of sodium transport and cyclic AMP by antidiuretic hormone after Ca2+ depletion of isolated frog skin epithelium. J Membr Biol. 1982;69(2):137–143. doi: 10.1007/BF01872273. [DOI] [PubMed] [Google Scholar]
  18. Kaminski J. J., Wallmark B., Briving C., Andersson B. M. Antiulcer agents. 5. Inhibition of gastric H+/K(+)-ATPase by substituted imidazo[1,2-a]pyridines and related analogues and its implication in modeling the high affinity potassium ion binding site of the gastric proton pump enzyme. J Med Chem. 1991 Feb;34(2):533–541. doi: 10.1021/jm00106a008. [DOI] [PubMed] [Google Scholar]
  19. Knowles M. R., Church N. L., Waltner W. E., Yankaskas J. R., Gilligan P., King M., Edwards L. J., Helms R. W., Boucher R. C. A pilot study of aerosolized amiloride for the treatment of lung disease in cystic fibrosis. N Engl J Med. 1990 Apr 26;322(17):1189–1194. doi: 10.1056/NEJM199004263221704. [DOI] [PubMed] [Google Scholar]
  20. Knowles M. R., Stutts M. J., Yankaskas J. R., Gatzy J. T., Boucher R. C., Jr Abnormal respiratory epithelial ion transport in cystic fibrosis. Clin Chest Med. 1986 Jun;7(2):285–297. [PubMed] [Google Scholar]
  21. Knowles M., Murray G., Shallal J., Askin F., Ranga V., Gatzy J., Boucher R. Bioelectric properties and ion flow across excised human bronchi. J Appl Physiol Respir Environ Exerc Physiol. 1984 Apr;56(4):868–877. doi: 10.1152/jappl.1984.56.4.868. [DOI] [PubMed] [Google Scholar]
  22. Kyle H., Ward J. P., Widdicombe J. G. Control of pH of airway surface liquid of the ferret trachea in vitro. J Appl Physiol (1985) 1990 Jan;68(1):135–140. doi: 10.1152/jappl.1990.68.1.135. [DOI] [PubMed] [Google Scholar]
  23. Lester D. S., Asher C., Garty H. Characterization of cAMP-induced activation of epithelial sodium channels. Am J Physiol. 1988 Jun;254(6 Pt 1):C802–C808. doi: 10.1152/ajpcell.1988.254.6.C802. [DOI] [PubMed] [Google Scholar]
  24. MATTHEWS L. W., SPECTOR S., LEMM J., POTTER J. L. STUDIES ON PULMONARY SECRETIONS. I. THE OVER-ALL CHEMICAL COMPOSITION OF PULMONARY SECRETIONS FROM PATIENTS WITH CYSTIC FIBROSIS, BRONCHIECTASIS, AND LARYNGECTOMY. Am Rev Respir Dis. 1963 Aug;88:199–204. doi: 10.1164/arrd.1963.88.2.199. [DOI] [PubMed] [Google Scholar]
  25. Mangoo-Karim R., Uchic M. E., Grant M., Shumate W. A., Calvet J. P., Park C. H., Grantham J. J. Renal epithelial fluid secretion and cyst growth: the role of cyclic AMP. FASEB J. 1989 Dec;3(14):2629–2632. doi: 10.1096/fasebj.3.14.2480260. [DOI] [PubMed] [Google Scholar]
  26. Marunaka Y., Eaton D. C. Effects of vasopressin and cAMP on single amiloride-blockable Na channels. Am J Physiol. 1991 May;260(5 Pt 1):C1071–C1084. doi: 10.1152/ajpcell.1991.260.5.C1071. [DOI] [PubMed] [Google Scholar]
  27. Melon J. Contribution à l'étude de l'activité sécrétoire de la muqqueuse nasale. Caractères de perméabilité de l'épithélium. Composition chimique du mucus. Le mécaanisme de sa formation dans les conditions normales et au cours des hypersécrtions paroxystiques. Acta Otorhinolaryngol Belg. 1968;22(1):5–244. [PubMed] [Google Scholar]
  28. Mentz W. M., Brown J. B., Friedman M., Stutts M. J., Gatzy J. T., Boucher R. C. Deposition, clearance, and effects of aerosolized amiloride in sheep airways. Am Rev Respir Dis. 1986 Nov;134(5):938–943. doi: 10.1164/arrd.1986.134.5.938. [DOI] [PubMed] [Google Scholar]
  29. Nielson D. W., Goerke J., Clements J. A. Alveolar subphase pH in the lungs of anesthetized rabbits. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7119–7123. doi: 10.1073/pnas.78.11.7119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Olver R. E., Davis B., Marin M. G., Nadel J. A. Active transport of Na+ and Cl- across the canine tracheal epithelium in vitro. Am Rev Respir Dis. 1975 Dec;112(6):811–815. doi: 10.1164/arrd.1975.112.6.811. [DOI] [PubMed] [Google Scholar]
  31. Olver R. E., Ramsden C. A., Strang L. B., Walters D. V. The role of amiloride-blockable sodium transport in adrenaline-induced lung liquid reabsorption in the fetal lamb. J Physiol. 1986 Jul;376:321–340. doi: 10.1113/jphysiol.1986.sp016156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Planelles G., Anagnostopoulos T., Cheval L., Doucet A. Biochemical and functional characterization of H(+)-K(+)-ATPase in distal amphibian nephron. Am J Physiol. 1991 Jun;260(6 Pt 2):F806–F812. doi: 10.1152/ajprenal.1991.260.6.F806. [DOI] [PubMed] [Google Scholar]
  33. Quinton P. M. Cystic fibrosis: a disease in electrolyte transport. FASEB J. 1990 Jul;4(10):2709–2717. doi: 10.1096/fasebj.4.10.2197151. [DOI] [PubMed] [Google Scholar]
  34. Robinson N. P., Kyle H., Webber S. E., Widdicombe J. G. Electrolyte and other chemical concentrations in tracheal airway surface liquid and mucus. J Appl Physiol (1985) 1989 May;66(5):2129–2135. doi: 10.1152/jappl.1989.66.5.2129. [DOI] [PubMed] [Google Scholar]
  35. Schlatter E., Schafer J. A. Electrophysiological studies in principal cells of rat cortical collecting tubules. ADH increases the apical membrane Na+-conductance. Pflugers Arch. 1987 Jun;409(1-2):81–92. doi: 10.1007/BF00584753. [DOI] [PubMed] [Google Scholar]
  36. Sleigh M. A., Blake J. R., Liron N. The propulsion of mucus by cilia. Am Rev Respir Dis. 1988 Mar;137(3):726–741. doi: 10.1164/ajrccm/137.3.726. [DOI] [PubMed] [Google Scholar]
  37. Smith J. J., Welsh M. J. cAMP stimulates bicarbonate secretion across normal, but not cystic fibrosis airway epithelia. J Clin Invest. 1992 Apr;89(4):1148–1153. doi: 10.1172/JCI115696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Smith P. L., Welsh M. J., Stoff J. S., Frizzell R. A. Chloride secretion by canine tracheal epithelium: I. Role of intracellular c AMP levels. J Membr Biol. 1982;70(3):217–226. doi: 10.1007/BF01870564. [DOI] [PubMed] [Google Scholar]
  39. Welsh M. J. Electrolyte transport by airway epithelia. Physiol Rev. 1987 Oct;67(4):1143–1184. doi: 10.1152/physrev.1987.67.4.1143. [DOI] [PubMed] [Google Scholar]
  40. Welsh M. J. Energetics of chloride secretion in canine tracheal epithelium. Comparison of the metabolic cost of chloride transport with the metabolic cost of sodium transport. J Clin Invest. 1984 Jul;74(1):262–268. doi: 10.1172/JCI111410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Welsh M. J. Ion transport by primary cultures of canine tracheal epithelium: methodology, morphology, and electrophysiology. J Membr Biol. 1985;88(2):149–163. doi: 10.1007/BF01868429. [DOI] [PubMed] [Google Scholar]
  42. Welsh M. J., Smith P. L., Frizzell R. A. Chloride secretion by canine tracheal epithelium: II. The cellular electrical potential profile. J Membr Biol. 1982;70(3):227–238. doi: 10.1007/BF01870565. [DOI] [PubMed] [Google Scholar]
  43. Welsh M. J., Smith P. L., Frizzell R. A. Chloride secretion by canine tracheal epithelium: III. Membrane resistances and electromotive forces. J Membr Biol. 1983;71(3):209–218. doi: 10.1007/BF01875462. [DOI] [PubMed] [Google Scholar]
  44. Welsh M. J., Widdicombe J. H., Nadel J. A. Fluid transport across the canine tracheal epithelium. J Appl Physiol Respir Environ Exerc Physiol. 1980 Nov;49(5):905–909. doi: 10.1152/jappl.1980.49.5.905. [DOI] [PubMed] [Google Scholar]
  45. Widdicombe J. H. Cystic fibrosis and beta-adrenergic response of airway epithelial cell cultures. Am J Physiol. 1986 Oct;251(4 Pt 2):R818–R822. doi: 10.1152/ajpregu.1986.251.4.R818. [DOI] [PubMed] [Google Scholar]
  46. Widdicombe J. H., Ueki I. F., Bruderman I., Nadel J. A. The effects of sodium substitution and ouabain on ion transport by dog tracheal epithelium. Am Rev Respir Dis. 1979 Aug;120(2):385–392. doi: 10.1164/arrd.1979.120.2.385. [DOI] [PubMed] [Google Scholar]
  47. Widdicombe J. H., Welsh M. J. Ion transport by dog tracheal epithelium. Fed Proc. 1980 Nov;39(13):3062–3066. [PubMed] [Google Scholar]
  48. Wu R., Yankaskas J., Cheng E., Knowles M. R., Boucher R. Growth and differentiation of human nasal epithelial cells in culture. Serum-free, hormone-supplemented medium and proteoglycan synthesis. Am Rev Respir Dis. 1985 Aug;132(2):311–320. doi: 10.1164/arrd.1985.132.2.311. [DOI] [PubMed] [Google Scholar]
  49. Yoneda K. Mucous blanket of rat bronchus: an ultrastructural study. Am Rev Respir Dis. 1976 Nov;114(5):837–842. doi: 10.1164/arrd.1976.114.5.837. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES