{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T15:02:46Z","timestamp":1785855766245,"version":"3.56.0"},"reference-count":61,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2017,6,11]],"date-time":"2017-06-11T00:00:00Z","timestamp":1497139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL\u2010108627"],"award-info":[{"award-number":["R01 HL\u2010108627"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL\u2010110539"],"award-info":[{"award-number":["R01 HL\u2010110539"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000070","name":"National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","award":["F31 EB\u2010018707"],"award-info":[{"award-number":["F31 EB\u2010018707"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2017,7,15]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\"><jats:list-item><jats:p>Hydrocortisone (HC) is required for activation of large\u2010conductance Ca<jats:sup>2+<\/jats:sup>\u2010activated K<jats:sup>+<\/jats:sup>current (BK) by purinergic receptor agonists.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>HC reduces insertion of the stress\u2010regulated exon (STREX) in the KCNMA1 gene, permitting protein kinase C (PKC)\u2010dependent channel activation.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Overlapping and unique purinergic signalling regions exist at the apical border of differentiated surface cells.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>BK channels localize in the cilia of surface cells.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>In the present study we investigated the role of hydrocortisone (HC) on uridine\u20105\u02b9\u2010triphosphate (UTP)\u2010stimulated ion transport in differentiated, pseudostratified epithelia derived from normal human bronchial basal cells. The presence of a UTP\u2010stimulated, paxilline\u2010sensitive large\u2010conductance Ca<jats:sup>2+<\/jats:sup>\u2010activated K<jats:sup>+<\/jats:sup>(BK) current was demonstrated in control epithelia but was not stimulated in epithelia differentiated in the absence of HC (HC0). Addition of the BK channel opener NS11021 directly activated channels in control epithelia; however, under HC0 conditions, activation only occurred when UTP was added after NS11021. The PKC inhibitors GF109203x and G\u00f66983 blocked BK activation by UTP in control epithelia, suggesting that PKC\u2010mediated phosphorylation plays a permissive role in purinoceptor\u2010stimulated BK activation. Moreover, HC0 epithelia expressed significantly more KCNMA1 containing the stress\u2010regulated exon (STREX), a splice\u2010variant of the \u03b1\u2010subunit that displays altered channel regulation by phosphorylation, compared to control epithelia. Furthermore, BK channels as well as purinergic receptors were shown to localize in unique and overlapping domains at the apical membrane of ciliated surface cells. These results establish a previously unrecognized role for glucocorticoids in regulation of BK channels in airway epithelial cells.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp274200","type":"journal-article","created":{"date-parts":[[2017,5,8]],"date-time":"2017-05-08T12:52:59Z","timestamp":1494247979000},"page":"4631-4645","source":"Crossref","is-referenced-by-count":16,"title":["Large\u2010conductance Ca<sup>2+<\/sup>\u2010activated K<sup>+<\/sup>channel activation by apical P2Y receptor agonists requires hydrocortisone in differentiated airway epithelium"],"prefix":"10.1113","volume":"595","author":[{"given":"Nathan A.","family":"Zaidman","sequence":"first","affiliation":[{"name":"Department of Integrative Biology and Physiology University of Minnesota 6\u2010125 Jackson Hall Minneapolis MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Panoskaltsis\u2010Mortari","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology 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