Functional apical large conductance, Ca2+-activated, and voltage-dependent K+ channels are required for maintenance of airway surface liquid volume.

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Title:	Functional apical large conductance, Ca2+-activated, and voltage-dependent K+ channels are required for maintenance of airway surface liquid volume.
Authors:	陳仁祥 Manzanares, Dahis Gonzalez, Carlos Ivonnet, Pedro Chen, Ren-Shiang Monica, Valencia-Gattas Gregory, E.Conner Larsson, H.Peter Salathe, Matthias
Contributors:	Division of Pulmonary and Critical Care, University of Miami Department of Physiology and Biophysics, University of Miami Department of Cell Biology and Anatomy, University of Miami Centro Interdisciplinario de Neurociencia, Universidad de Valparaiso
Keywords:	Anion Transport Epithelium, Lung Potassium Channels shRNA Airway Surface Liquid Cilia
Date:	2011-06
Issue Date:	2016-11-24T01:15:04Z (UTC)
Publisher:	US: American Society for Biochemistry and Molecular Biology
Abstract:	Large conductance, Ca2+-activated, and voltage-dependent K+ (BK) channels control a variety of physiological processes in nervous, muscular, and renal epithelial tissues. In bronchial airway epithelia, extracellular ATP-mediated, apical increases in intracellular Ca2+ are important signals for ion movement through the apical membrane and regulation of water secretion. Although other, mainly basolaterally expressed K+ channels are recognized as modulators of ion transport in airway epithelial cells, the role of BK in this process, especially as a regulator of airway surface liquid volume, has not been examined. Using patch clamp and Ussing chamber approaches, this study reveals that BK channels are present and functional at the apical membrane of airway epithelial cells. BK channels open in response to ATP stimulation at the apical membrane and allow K+ flux to the airway surface liquid, whereas no functional BK channels were found basolaterally. Ion transport modeling supports the notion that apically expressed BK channels are part of an apical loop current, favoring apical Cl− efflux. Importantly, apical BK channels were found to be critical for the maintenance of adequate airway surface liquid volume because continuous inhibition of BK channels or knockdown of KCNMA1, the gene coding for the BK α subunit (KCNMA1), lead to airway surface dehydration and thus periciliary fluid height collapse revealed by low ciliary beat frequency that could be fully rescued by addition of apical fluid. Thus, apical BK channels play an important, previously unrecognized role in maintaining adequate airway surface hydration.
Relation:	The Journal of biological chemistry, 286(22), 19830-19839
Appears in Collections:	[生命科學系所] 期刊論文

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