{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T08:22:19Z","timestamp":1774686139346,"version":"3.50.1"},"reference-count":54,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2014,3,15]]},"abstract":"<jats:p> KCNQ (Kv7 family) potassium (K<jats:sup>+<\/jats:sup>) channels were recently found in airway smooth muscle cells (ASMCs) from rodent and human bronchioles. In the present study, we evaluated expression of KCNQ channels and their role in constriction\/relaxation of rat airways. Real-time RT-PCR analysis revealed expression of KCNQ4 &gt; KCNQ5 &gt; KCNQ1 &gt; KCNQ2 &gt; KCNQ3, and patch-clamp electrophysiology detected KCNQ currents in rat ASMCs. In precision-cut lung slices, the KCNQ channel activator retigabine induced a concentration-dependent relaxation of small bronchioles preconstricted with methacholine (MeCh; EC<jats:sub>50<\/jats:sub> = 3.6 \u00b1 0.3 \u03bcM). Bronchoconstriction was also attenuated in the presence of two other structurally unrelated KCNQ channel activators: zinc pyrithione (ZnPyr; 1 \u03bcM; 22 \u00b1 7%) and 2,5-dimethylcelecoxib (10 \u03bcM; 24 \u00b1 8%). The same three KCNQ channel activators increased KCNQ currents in ASMCs by two- to threefold. The bronchorelaxant effects of retigabine and ZnPyr were prevented by inclusion of the KCNQ channel blocker XE991. A long-acting \u03b2<jats:sub>2<\/jats:sub>-adrenergic receptor agonist, formoterol (10 nM), did not increase KCNQ current amplitude in ASMCs, but formoterol (1\u20131,000 nM) did induce a time- and concentration-dependent relaxation of rat airways, with a notable desensitization during a 30-min treatment or with repetitive treatments. Coadministration of retigabine (10 \u03bcM) with formoterol produced a greater peak and sustained reduction of MeCh-induced bronchoconstriction and reduced the apparent desensitization observed with formoterol alone. Our findings support a role for KCNQ K<jats:sup>+<\/jats:sup> channels in the regulation of airway diameter. A combination of a \u03b2<jats:sub>2<\/jats:sub>-adrenergic receptor agonist with a KCNQ channel activator may improve bronchodilator therapy. <\/jats:p>","DOI":"10.1152\/ajplung.00253.2013","type":"journal-article","created":{"date-parts":[[2014,1,18]],"date-time":"2014-01-18T01:30:37Z","timestamp":1390008637000},"page":"L476-L486","source":"Crossref","is-referenced-by-count":24,"title":["KCNQ (Kv7) potassium channel activators as bronchodilators: combination with a \u03b2<sub>2<\/sub>-adrenergic agonist enhances relaxation of rat airways"],"prefix":"10.1152","volume":"306","author":[{"given":"Lioubov I.","family":"Brueggemann","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology and Therapeutics, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer M.","family":"Haick","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology and 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