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CFTR correctors are therapeutics that restore the folding\/trafficking of mutated CFTR to the plasma membrane. The large-conductance calcium-activated potassium channel (BK\n                    <jats:sub>Ca<\/jats:sub>\n                    , K\n                    <jats:sub>Ca<\/jats:sub>\n                    1.1) is also critical for maintaining lung airway surface liquid (ASL) volume. Here, we show that the class 2 (C2) CFTR corrector VX-445 (elexacaftor) induces K\n                    <jats:sup>+<\/jats:sup>\n                    secretion across WT and F508del CFTR primary human bronchial epithelial cells (HBEs), which was entirely inhibited by the BK\n                    <jats:sub>Ca<\/jats:sub>\n                    antagonist paxilline. Similar results were observed with VX-121, a corrector under clinical evaluation. Whole-cell patch-clamp recordings verified that CFTR correctors potentiated BK\n                    <jats:sub>Ca<\/jats:sub>\n                    activity from both primary HBEs and HEK cells stably expressing the \u03b1 subunit (HEK-BK cells). Furthermore, excised patch-clamp recordings from HEK-BK cells verified direct action on the channel and demonstrated a significant increase in open probability. In mouse mesenteric artery, VX-445 induced a paxilline-sensitive vasorelaxation of preconstricted arteries. VX-445 also reduced firing frequency in primary rat hippocampal and cortical neurons. We raise the possibilities that C2 CFTR correctors gain additional clinical benefit by activation of BK\n                    <jats:sub>Ca<\/jats:sub>\n                    in the lung yet may lead to adverse events through BK\n                    <jats:sub>Ca<\/jats:sub>\n                    activation elsewhere.\n                  <\/jats:p>","DOI":"10.1172\/jci176328","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T12:00:58Z","timestamp":1719921658000},"source":"Crossref","is-referenced-by-count":17,"title":["Potentiation of BKCa channels by cystic fibrosis transmembrane conductance regulator correctors VX-445 and VX-121"],"prefix":"10.1172","volume":"134","author":[{"given":"Aaron","family":"Kolski-Andreaco","sequence":"first","affiliation":[{"name":"Department of Cell Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Taiclet","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael M.","family":"Myerburg","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Sembrat","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Bridges","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Chicago Medical School, North Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam C.","family":"Straub","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary P.","family":"Wills","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Butterworth","sequence":"additional","affiliation":[{"name":"Department of Cell Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.","family":"Devor","sequence":"additional","affiliation":[{"name":"Department of Cell Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2024,7,2]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","unstructured":"Cheema ZM, et al. 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