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

Dahis Manzanares, Carlos Gonzalez, Pedro Ivonnet, Ren Shiang Chen, Monica Valencia-Gattas, Gregory E Conner, Hans P Larsson, Matthias A Salathe

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)19830-19839
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number22
DOIs
StatePublished - Jun 3 2011

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Large-Conductance Calcium-Activated Potassium Channels
Maintenance
Liquids
Electric potential
Ion Transport
Ions
Membranes
Epithelium
Adenosine Triphosphate
Epithelial Cells
Physiological Phenomena
Gene Knockdown Techniques
Fluids
Clamping devices
Dehydration
Hydration
Modulators
Genes
Tissue
Fluxes

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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Functional apical large conductance, Ca2+-activated, and voltage-dependent K+ channels are required for maintenance of airway surface liquid volume. / Manzanares, Dahis; Gonzalez, Carlos; Ivonnet, Pedro; Chen, Ren Shiang; Valencia-Gattas, Monica; Conner, Gregory E; Larsson, Hans P; Salathe, Matthias A.

In: Journal of Biological Chemistry, Vol. 286, No. 22, 03.06.2011, p. 19830-19839.

Research output: Contribution to journalArticle

Manzanares, Dahis ; Gonzalez, Carlos ; Ivonnet, Pedro ; Chen, Ren Shiang ; Valencia-Gattas, Monica ; Conner, Gregory E ; Larsson, Hans P ; Salathe, Matthias A. / Functional apical large conductance, Ca2+-activated, and voltage-dependent K+ channels are required for maintenance of airway surface liquid volume. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 22. pp. 19830-19839.
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