Role of CFTR in chloride secretion across human tracheal epithelium

B. Q. Shen, R. J. Mrsny, W. E. Finkbeiner, Jonathan Widdicombe

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

We have tested two hypotheses: 1) the cystic fibrosis transmembrane conductance regulator (CFTR) represents the predominant Cl conductance in the apical membrane of human tracheal epithelium, and 2) CFTR in this tissue is close to maximally activated under baseline conditions. In support of the first hypothesis, we found 1) when the level of differentiation of cultures was varied by varying the culture conditions, there was a significant positive correlation between the levels of CFTR and the magnitude of mediator-induced Cl secretion. 2) Amiloride-insensitive baseline short- circuit current (I(sc)) and mediator-induced increases in 1(sc) were inhibited by diphenylamine-2-carboxylic acid (DPAC) but not by 4,4'- diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), a pharmacology consistent with passage of apical membrane Cl current through CFTR; Ca-activated Cl channels are inhibited by DIDS but not by DPAC. 3) Raising temperature from 22° to 37°C increased 125I efflux, and this increase was inhibited by DPAC and blockers of protein kinase A, but not by DIDS or 1,2-bis(2- aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester. In support of the second hypothesis, we have earlier shown [M. Yamaya, W. E. Finkbeiner, S. Y. Chun, and J. H. Widdicombe. Am. J. Physiol. 262 (Lung Cell. Mol. Physiol. 6): L713-L724, 1992] that adenosine 3',5'-cyclic monophosphate (cAMP)elevating agents are essentially without effect on I(sc) across primary cultures of human tracheal epithelium. Here, we further show that these agents are also usually without effect on 125I efflux; the mean increase in efflux in response to elevating cAMP was ~20% that of raising temperature from 22° to 37°C.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume269
Issue number5 13-5
StatePublished - 1995

Keywords

  • airway epithelium
  • cell culture
  • cystic fibrosis

ASJC Scopus subject areas

  • Cell Biology
  • Physiology
  • Pulmonary and Respiratory Medicine
  • Agricultural and Biological Sciences(all)

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