Chloride channels in the airways are especially abundant in the surface epithelium and gland compartments where they play an essential role in the transepithelial movement of electrolytes and water. The cystic fibrosis transmembrane conductance regulator, a member of the superfamily of ATP-binding cassette transport proteins, functions as a cyclic AMP- and cyclic GMP-activated chloride channel and is a major determinant of airway fluid homeostasis by triple action: it inhibits isotonic NaCl and fluid absorption by the ciliated cells through its interaction with epithelial sodium channels, it promotes fluid secretion by serous cells in the submucosal glands, and it mediates beta;-adrenergic stimulation of NaCl and fluid absorption in the distal airways and alveolar compartment. Consequently, CF airways show a depletion of airway surface liquid resulting in impaired mucociliary clearance, and a propensity to pulmonary edema. Calcium-activated chloride channels are abundantly expressed in tracheal and bronchial epithelium. Upon activation by Ca 2+-mobilizing, purinergic, or cholinergic receptors, they may serve as compensatory chloride channels in CF. Their molecular nature is not yet elucidated. Putative molecular candidates include the CLCAs (hCLCA1-4). hCLCA1 (gob-5) is associated with mucin granule membranes and plays a key role in mucus overproduction and the pathogenesis of bronchial asthma. In addition, numerous other chloride channel species (e.g., CLCs, bestrophins, CLICs, and ORCCs) have been identified in the respiratory tract and are briefly discussed in this review.

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Keywords Airway surface liquid, Bestrophin, Calcium-activated chloride channels, Chloride channel, Chloride channel families, Chloride intracellular channels, CLC family, Cystic fibrosis transmembrane conductance regulator, Transepithelial movement
Persistent URL dx.doi.org/10.1016/B0-12-370879-6/00201-5, hdl.handle.net/1765/118334
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Citation
de Jonge, H.R, & Tilly, B.C. (2006). Ion Transport: Chloride Channels. In Encyclopedia of Respiratory Medicine, Four-Volume Set (pp. 465–471). doi:10.1016/B0-12-370879-6/00201-5