Role of K(V)LQT1 in cyclic adenosine monophosphate-mediated C1- secretion in human airway epithelia

Mall, Marcus, Wissner, Andreas, Schreiber, Rainer, Kuehr, Joachim, Seydewitz, Hans H., Brandis, Matthias, Greger, Rainer and Kunzelmann, Karl H. P. (2000) Role of K(V)LQT1 in cyclic adenosine monophosphate-mediated C1- secretion in human airway epithelia. American Journal of Respiratory Cell and Molecular Biology, 23 3: 283-289.

Author Mall, Marcus
Wissner, Andreas
Schreiber, Rainer
Kuehr, Joachim
Seydewitz, Hans H.
Brandis, Matthias
Greger, Rainer
Kunzelmann, Karl H. P.
Title Role of K(V)LQT1 in cyclic adenosine monophosphate-mediated C1- secretion in human airway epithelia
Formatted title
Role of KVLQT1 in cyclic adenosine monophosphate-mediated Cl secretion in human airway epithelia
Journal name American Journal of Respiratory Cell and Molecular Biology   Check publisher's open access policy
ISSN 1044-1549
Publication date 2000-09-01
Sub-type Article (original research)
Open Access Status Not Open Access
Volume 23
Issue 3
Start page 283
End page 289
Total pages 7
Place of publication New York, NY, U.S.A.
Publisher American Thoracic Society
Language eng
Subject C1
270104 Membrane Biology
730110 Respiratory system and diseases (incl. asthma)
Formatted abstract
Ion transport defects underlying cystic fibrosis (CF) lung disease are characterized by impaired cyclic adenosine monophosphate (cAMP)-dependent Cl conductance. Activation of Cl secretion in airways depends on simultaneous activation of luminal Cl channels and basolateral K+ channels. We determined the role of basolateral K+ conductance in cAMP-dependent Cl secretion in native human airway epithelium obtained from non-CF and CF patients. CF tissues showed typical alterations of short-circuit currents with enhanced amiloride-sensitive Na+ conductance and defective cAMP-mediated Cl conductance. In non-CF tissues, Cl secretion was significantly inhibited by the chromanol 293B (10 µmol/liter), a specific inhibitor of KVLQT1 K+ channels. Inhibition was increased after cAMP-dependent stimulation. Similar effects were obtained with Ba2+ (5 μmol/liter). In patch-clamp experiments with a human bronchial epithelial cell line, stimulation with forskolin (10 µmol/liter) simultaneously activated Cl and K+ conductance. The K+ conductance was reversibly inhibited by Ba2+ and 293B. Analysis of reverse-transcribed messenger RNA from non-CF and CF airways showed expression of human KVLQT1. We conclude that the K+ channel KVLQT1 is important in maintaining cAMP-dependent Cl secretion in human airways. Activation of KVLQT1 in CF airways in parallel with stimulation of residual CF transmembrane conductance regulator Cl channel activity or alternative Cl channels could help to circumvent the secretory defect.
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Pharmacy Publications
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Created: Tue, 10 Jun 2008, 21:33:35 EST