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Chloride transport in cultured nasal epithelium of cystic fibrosis patients
Authors:Elly Verbeek  Hugo R. de Jonge  Jan Bijman  Joke Keulemans  Maarten Sinaasappel  Arthur W. M. van der Kamp  Bob J. Scholte
Affiliation:(1) Department of Cell Biology and Genetics, Erasmus Universiteit, P/O box 1738, NL-3000 DR Rotterdam, The Netherlands;(2) Department of Biochemistry I, Erasmus Universiteit, P/O box 1738, NL-3000 DR Rotterdam, The Netherlands;(3) Department of Pediatrics, Erasmus Universiteit, P/O box 1738, NL-3000 DR Rotterdam, The Netherlands
Abstract:In this study, nasal polyp epithelial cells from control and cystic fubrosis (CF) patients were cultured using a method which allows multiple passages. The cells were tested in Ussing chamber experiments to study transcellular ion transport. Cultured CF nasal polyp cells did not exhibit spontaneous transcellular chloride transport in the presence of amiloride, in contrast to normal cells. Forskolin increased the short circuit current (I sc) in control but not CF cells. Forskolin and isoproterenol increased the cAMP levels in control and CF cells. Histamine, bradykinin and isoproterenol transiently increased the intracellular calcium level and caused a parallel increase of the transcellular chloride current in both normal and CF cells. The transient effects of isoproterenol were not sensitive to the beta blocker atenol and could not be mimicked by forskolin. We conclude that in cultured nasal polyp cells a difference in chloride transport activity between CF and control cells is retained following multiple passages. Our results suggest that the active state of chloride channels in nasal polyp cells does not require activation of a second messenger pathway. This apparently spontaneous activity appears to be reduced in CF cells. The calcium- but not the cAMP-dependent activation of transepithelial chloride secretion is at least partially preserved in cultured CF airway epithelium.
Keywords:Cystic fibrosis  Chloride transport
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