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Glucocorticoid Regulation of Large Conductance, Ca 2+ ‐Activated K Channels in Differentiated Human Bronchial Epithelial Cells
Author(s) -
Zaidman Nathan A,
PanoskaltsisMortari Angela,
O'Grady Scott M
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1007.28
Subject(s) - bk channel , chemistry , phosphorylation , microbiology and biotechnology , medicine , endocrinology , biology , membrane potential , biochemistry
An important component of airway host‐defense involves the process of trapping and removing inspired material through mucociliary clearance (MCC). Regulated transepithelial ion transport supports this process by maintaining the depth of the airway surface liquid (ASL). In the present study we determined the effects of hydrocortisone (HC) on UTP‐stimulated ion transport in differentiated, pseudostratified epithelia derived from normal human bronchial basal cells. UTP stimulated a paxilline‐sensitive, large conductance Ca 2+ ‐activated K (BK) current in control epithelia differentiated in HC containing media, however BK current was not detected in epithelia differentiated in the absence of HC (HC0). The BK opener NS11021 directly activated channels in control epithelia, but in the absence of HC, BK current was only observed when UTP was added after NS11021. The pan‐specific PKC inhibitors GF109203× and Gö6983 blocked UTP‐induced BK activation under control conditions, suggesting that PKC‐mediated phosphorylation was necessary for BK activation. HC0 epithelia expressed significantly more KCNMA1 mRNA transcripts containing the stress‐regulated exon (STREX), a splice‐variant that exhibits altered channel regulation by phosphorylation relative to channels that do not contain the STREX sequence. Furthermore, BK channels and P2Y receptors exhibited distinct cellular localization patterns in overlapping membrane domains at the apical region of differentiated surface cells. These results demonstrate a previously unrecognized role for glucocorticoids in BK channel regulation. Support or Funding Information This work was supported by National Institute of Biomedical Imaging and Bioengineering Grant F31 EB‐018707 (N. A. Zaidman) and National Heart, Lung, and Blood Institute Grants R01 HL‐108627 (A. Panoskaltsis‐Mortari) and R01 HL‐110539 (S. M. O'Grady)