{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T02:03:35Z","timestamp":1792721015107,"version":"4.5.0"},"reference-count":52,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2014,3,1]]},"abstract":"<jats:p> 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<jats:sup>2+<\/jats:sup>-activated, and voltage-dependent K<jats:sup>+<\/jats:sup> (BK) channels provide an electrochemical gradient for Cl<jats:sup>\u2212<\/jats:sup> secretion and thus play an important role for adequate airway hydration. Here we show that IFN-\u03b3 decreases ATP-mediated apical BK activation in normal human airway epithelial cells cultured at the air-liquid interface. IFN-\u03b3 decreased mRNA levels of KCNMA1 but did not affect total protein levels. Because IFN-\u03b3 upregulates dual oxidase (DUOX)2 and therefore H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> production, we hypothesized that BK inactivation could be mediated by BK oxidation. However, DUOX2 knockdown did not affect the IFN-\u03b3 effect on BK activity. IFN-\u03b3 changed mRNA levels of the BK \u03b2-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-\u03b3 treatment. Finally, IFN-\u03b3 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-\u03b3. Key experiments were repeated in cystic fibrosis cells and showed the same results. Therefore, IFN-\u03b3 induces mucociliary dysfunction through BK inactivation. <\/jats:p>","DOI":"10.1152\/ajplung.00247.2013","type":"journal-article","created":{"date-parts":[[2014,1,11]],"date-time":"2014-01-11T02:02:06Z","timestamp":1389405726000},"page":"L453-L462","source":"Crossref","is-referenced-by-count":48,"title":["IFN-\u03b3-mediated reduction of large-conductance, Ca<sup>2+<\/sup>-activated, voltage-dependent K<sup>+<\/sup> (BK) channel activity in airway epithelial cells leads to mucociliary dysfunction"],"prefix":"10.1152","volume":"306","author":[{"given":"Dahis","family":"Manzanares","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine 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