ArticleAmerican journal of physiology. Lung cellular and molecular physiology2014
IFN-γ-mediated reduction of large-conductance, Ca2+-activated, voltage-dependent K+ (BK) channel activity in airway epithelial cells leads to mucociliary dysfunction.
Article in American journal of physiology. Lung cellular and molecular physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 45 citations in OpenAlex.
- Effect of glabridin on ion transport across primary human bronchial epithelial cells.American journal of physiology. Cell physiology · 2026Article
- Pharmacological Relevance of β-, γ-, and LINGO Auxiliary Subunits in BK Channel Modulation.ChemMedChem · 2026Review
- VX-445 (elexacaftor) inhibits chloride secretion across human bronchial epithelial cells by directly blocking KCa3.1 channels.PNAS nexus · 2025Article
- Therapeutic strategies to reverse cigarette smoke-induced ion channel and mucociliary dysfunction in COPD airway epithelial cells.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Cystic fibrosis.Nature reviews. Disease primers · 2024Review
- Potentiation of BKCa channels by cystic fibrosis transmembrane conductance regulator correctors VX-445 and VX-121.The Journal of clinical investigation · 2024Article
- The combination of propylene glycol and vegetable glycerin e-cigarette aerosols induces airway inflammation and mucus hyperconcentration.Scientific reports · 2024Article
- The role of potassium ion channels in chronic sinusitis.Frontiers in pharmacology · 2024Review
- E-cigarette aerosols of propylene glycol impair BK channel activity and parameters of mucociliary function.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- The LRRC family of BK channel regulatory subunits: potential roles in health and disease.The Journal of physiology · 2022Review
- Revisiting the Large-Conductance Calcium-Activated Potassium (BKCa) Channels in the Pulmonary Circulation.Biomolecules · 2021Review
- Hyperglycaemia in cystic fibrosis adversely affects BK channel function critical for mucus clearance.The European respiratory journal · 2021Article
- The Role of MicroRNA in the Airway Surface Liquid Homeostasis.International journal of molecular sciences · 2020Review
- Roles of LRRC26 as an auxiliary γ1-subunit of large-conductance CaAmerican journal of physiology. Lung cellular and molecular physiology · 2020Article
- Review
- Regulation of BK Channels by Beta and Gamma Subunits.Annual review of physiology · 2019Review
- The Effects of the Anti-aging Protein Klotho on Mucociliary Clearance.Frontiers in medicine · 2019Article
- ATP12A promotes mucus dysfunction during Type 2 airway inflammation.Scientific reports · 2018Article
- Ion channels of the lung and their role in disease pathogenesis.American journal of physiology. Lung cellular and molecular physiology · 2017Review
- Role of Smad3 and p38 Signalling in Cigarette Smoke-induced CFTR and BK dysfunction in Primary Human Bronchial Airway Epithelial Cells.Scientific reports · 2017Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Effective mucociliary clearance (MCC) depends in part on adequate airway surface liquid (ASL) volume to maintain an appropriate periciliary fluid height that allows normal ciliary activity. Apically expressed large-conductance, Ca(2+)-activated, and voltage-dependent K(+) (BK) channels provide an electrochemical gradient for Cl(-) secretion and thus play an important role for adequate airway hydration. Here we show that IFN-γ decreases ATP-mediated apical BK activation in normal human airway epithelial cells cultured at the air-liquid interface. IFN-γ decreased mRNA levels of KCNMA1 but did not affect total protein levels. Because IFN-γ upregulates dual oxidase (DUOX)2 and therefore H2O2 production, we hypothesized that BK inactivation could be mediated by BK oxidation. However, DUOX2 knockdown did not affect the IFN-γ effect on BK activity. IFN-γ changed mRNA levels of the BK β-modulatory proteins KCNMB2 (increased) and KCNMB4 (decreased) as well as leucine-rich repeat-containing protein (LRRC)26 (decreased). Mallotoxin, a BK opener only in the absence of LRRC26, showed that BK channels lost their association with LRRC26 after IFN-γ treatment. Finally, IFN-γ caused a decrease in ciliary beating frequency that was immediately rescued by apical fluid addition, suggesting that it was due to ASL volume depletion. These data were confirmed with direct ASL measurements using meniscus scanning. Overexpression of KCNMA1, the pore-forming subunit of BK, overcame the reduction of ASL volume induced by IFN-γ. Key experiments were repeated in cystic fibrosis cells and showed the same results. Therefore, IFN-γ induces mucociliary dysfunction through BK inactivation.
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