{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:01:53Z","timestamp":1792814513902,"version":"4.5.0"},"reference-count":50,"publisher":"National Academy of Sciences","issue":"4","license":[{"start":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T00:00:00Z","timestamp":1673913600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HD069631"],"award-info":[{"award-number":["R01 HD069631"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R33 HD099742"],"award-info":[{"award-number":["R33 HD099742"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Male Contraceptive Initiative","award":["2019-B01"],"award-info":[{"award-number":["2019-B01"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,1,24]]},"abstract":"<jats:p>\n                    To fertilize an oocyte, the membrane potential of both mouse and human sperm must hyperpolarize (become more negative inside). Determining the molecular mechanisms underlying this hyperpolarization is vital for developing new contraceptive methods and detecting causes of idiopathic male infertility. In mouse sperm, hyperpolarization is caused by activation of the sperm-specific potassium (K\n                    <jats:sup>+<\/jats:sup>\n                    ) channel SLO3 [C. M. Santi\u00a0\n                    <jats:italic>et\u00a0al.<\/jats:italic>\n                    ,\u00a0\n                    <jats:italic>FEBS Lett.<\/jats:italic>\n                    <jats:bold>584<\/jats:bold>\n                    , 1041\u20131046 (2010)]. In human sperm, it has long been unclear whether hyperpolarization depends on SLO3 or the ubiquitous K\n                    <jats:sup>+<\/jats:sup>\n                    channel SLO1 [N. Mannowetz, N. M. Naidoo, S. A. S. Choo, J. F. Smith, P. V. Lishko,\n                    <jats:italic>Elife<\/jats:italic>\n                    \u00a0\n                    <jats:bold>2<\/jats:bold>\n                    , e01009 (2013), C. Brenker\u00a0\n                    <jats:italic>et al.<\/jats:italic>\n                    ,\u00a0\n                    <jats:italic>Elife<\/jats:italic>\n                    <jats:bold>3<\/jats:bold>\n                    , e01438 (2014), and\u00a0S. A. Mansell, S. J. Publicover, C. L. R. Barratt, S. M. Wilson,\u00a0\n                    <jats:italic>Mol. Hum. Reprod.<\/jats:italic>\n                    <jats:bold>20<\/jats:bold>\n                    , 392\u2013408 (2014)]. In this work, we identified the first selective inhibitor for human SLO3\u2014VU0546110\u2014and showed that it completely blocked heterologous SLO3 currents and endogenous K\n                    <jats:sup>+<\/jats:sup>\n                    currents in human sperm. This compound also prevented sperm from hyperpolarizing and undergoing hyperactivated motility and induced acrosome reaction, which are necessary to fertilize an egg. We conclude that SLO3 is the sole K\n                    <jats:sup>+<\/jats:sup>\n                    channel responsible for hyperpolarization and significantly contributes to the fertilizing ability of human sperm. Moreover, SLO3 is a good candidate for contraceptive development, and mutation of this gene is a possible cause of idiopathic male infertility.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2212338120","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T16:46:31Z","timestamp":1673973991000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":45,"title":["A selective inhibitor of the sperm-specific potassium channel SLO3 impairs human sperm function"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2930-1726","authenticated-orcid":false,"given":"Maximilian","family":"Lyon","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8175-9067","authenticated-orcid":false,"given":"Juan J.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0177-2961","authenticated-orcid":false,"given":"Roman M.","family":"Lazarenko","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4002-3824","authenticated-orcid":false,"given":"Sujay V.","family":"Kharade","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"Kramer","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1792-9700","authenticated-orcid":false,"given":"Samantha J.","family":"McClenahan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Days","sequence":"additional","affiliation":[{"name":"Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua A.","family":"Bauer","sequence":"additional","affiliation":[{"name":"Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4172-4147","authenticated-orcid":false,"given":"Brittany D.","family":"Spitznagel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6886-1195","authenticated-orcid":false,"given":"C. David","family":"Weaver","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt University, Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9493-8387","authenticated-orcid":false,"given":"Aluet","family":"Borrego Alvarez","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lis C.","family":"Puga Molina","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Lybaert","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO 63110"},{"name":"Laboratoire de recherche 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