{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T20:33:23Z","timestamp":1758400403953,"version":"3.37.3"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T00:00:00Z","timestamp":1636934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HD037831"],"award-info":[{"award-number":["R01 HD037831"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Washington University Department of Obstetrics and Gynecology"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,19]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nuclear factor kappa B (NF-\u03baB) transcriptionally regulates several genes involved in initiating uterine contractions. A key factor controlling NF-\u03baB activity is its translocation to the nucleus. In myometrial smooth muscle cells (MSMCs), this translocation can be stimulated by the inflammatory molecule lipopolysaccharide (LPS) or by blocking the potassium calcium-activated channel subfamily M alpha 1 (KCNMA1 or BKCa) with paxilline (PAX). Here, we sought to determine the mechanism by which blocking BKCa causes NF-\u03baB-p65 translocation to the nucleus in MSMCs. We show that LPS- and PAX-induced NF-\u03baB-p65 translocation are similar in that neither depends on several mitogen-activated protein kinase pathways, but both require increased intracellular calcium (Ca2+). However, the nuclear transport inhibitor wheat germ agglutinin prevented NF-\u03baB-p65 nuclear translocation in response to LPS but not in response to PAX. Blocking BKCa located on the plasma membrane resulted in a transient NF-\u03baB-p65 nuclear translocation that was not sufficient to induce expression of its transcriptional target, suggesting a role for intracellular BKCa. We report that BKCa also localizes to the nucleus and that blocking nuclear BKCa results in an increase in nuclear Ca2+ in MSMCs. Together, these data suggest that BKCa localized on the nuclear membrane plays a key role in regulating nuclear Ca2+ and NF-\u03baB-p65 nuclear translocation in MSMCs.<\/jats:p>","DOI":"10.1093\/biolre\/ioab211","type":"journal-article","created":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T03:35:02Z","timestamp":1637206502000},"page":"441-448","source":"Crossref","is-referenced-by-count":5,"title":["Blocking the BKCa channel induces NF-\u03baB nuclear translocation by increasing nuclear calcium concentration"],"prefix":"10.1093","volume":"106","author":[{"given":"Lindsey N","family":"Kent","sequence":"first","affiliation":[{"name":"Center for Reproductive Health Sciences, Department of Obstetrics and Gynecology, Washington University in St. Louis, St. Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youe","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Reproductive Health Sciences, Department of Obstetrics and Gynecology, Washington University in St. Louis, St. Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monali","family":"Wakle-Prabagaran","sequence":"additional","affiliation":[{"name":"Center for Reproductive Health Sciences, Department of Obstetrics and Gynecology, Washington University in St. Louis, St. Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mashal Z","family":"Naqvi","sequence":"additional","affiliation":[{"name":"Center for Reproductive Health Sciences, Department of Obstetrics and Gynecology, Washington University in St. Louis, St. Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophia G","family":"Weil","sequence":"additional","affiliation":[{"name":"Center for Reproductive Health Sciences, Department of Obstetrics and Gynecology, Washington University in St. Louis, St. Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah K","family":"England","sequence":"additional","affiliation":[{"name":"Center for Reproductive Health Sciences, Department of Obstetrics and Gynecology, Washington University in St. Louis, St. Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,11,15]]},"reference":[{"key":"2022032101284038800_ref1","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1203\/00006450-199811000-00001","article-title":"Regulation of uterine smooth muscle function during gestation","volume":"44","author":"Riemer","year":"1998","journal-title":"Pediatr Res"},{"key":"2022032101284038800_ref2","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1038\/nn.3744","article-title":"Nuclear BK channels regulate gene expression via the control of nuclear calcium signaling","volume":"17","author":"Li","year":"2014","journal-title":"Nat Neurosci"},{"key":"2022032101284038800_ref3","first-page":"29","article-title":"Potassium 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