10970817

pubmed:Citation

3

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 micromol/liter), a specific inhibitor of K(V)LQT1 K(+) channels. Inhibition was increased after cAMP-dependent stimulation. Similar effects were obtained with Ba(2+) (5 mmol/liter). In patch-clamp experiments with a human bronchial epithelial cell line, stimulation with forskolin (10 micromol/liter) simultaneously activated Cl(-) and K(+) conductance. The K(+) conductance was reversibly inhibited by Ba(2+) and 293B. Analysis of reverse-transcribed messenger RNA from non-CF and CF airways showed expression of human K(V)LQT1. We conclude that the K(+) channel K(V)LQT1 is important in maintaining cAMP-dependent Cl(-) secretion in human airways. Activation of K(V)LQT1 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.

eng

IM

MEDLINE

1044-1549

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NLM

283-9

pubmed-meshheading:10970817-1-Methyl-3-isobutylxanthine, pubmed-meshheading:10970817-Amiloride, pubmed-meshheading:10970817-Biological Transport, pubmed-meshheading:10970817-Bronchi, pubmed-meshheading:10970817-Cell Line, Transformed, pubmed-meshheading:10970817-Chlorides, pubmed-meshheading:10970817-Chromans, pubmed-meshheading:10970817-Cyclic AMP, pubmed-meshheading:10970817-Cystic Fibrosis, pubmed-meshheading:10970817-Cystic Fibrosis Transmembrane Conductance Regulator, pubmed-meshheading:10970817-Diuretics, pubmed-meshheading:10970817-Forskolin, pubmed-meshheading:10970817-Gene Expression, pubmed-meshheading:10970817-Humans, pubmed-meshheading:10970817-KCNQ Potassium Channels, pubmed-meshheading:10970817-KCNQ1 Potassium Channel, pubmed-meshheading:10970817-Membrane Potentials, pubmed-meshheading:10970817-Patch-Clamp Techniques, pubmed-meshheading:10970817-Phosphodiesterase Inhibitors, pubmed-meshheading:10970817-Potassium, pubmed-meshheading:10970817-Potassium Channel Blockers, pubmed-meshheading:10970817-Potassium Channels, pubmed-meshheading:10970817-Potassium Channels, Voltage-Gated, pubmed-meshheading:10970817-Respiratory Mucosa, pubmed-meshheading:10970817-Sulfonamides

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

Journal Article, Research Support, Non-U.S. Gov't