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Extending the window of sperm capacitation could therefore increase sperm lifespan, prolong sperm-fertilizing competence and increase AI efficiency. Hyperpolarization of sperm is a crucial step in capacitation and is induced by activation of the potassium calcium-activated channel subfamily U member 1 (KCNU1, also named Slo3 or KSper). Given the essential role played by KCNU1 in capacitation, this study assessed the impact of its pharmacological inhibition on sperm lifespan. We showed that treatment of murine sperm with sub-micromolar concentrations of clofilium, a specific inhibitor of KCNU1, slowed down capacitation, decreased the rate of acrosome reaction and extended the fertilizing competence of capacitated sperm for 12\u2009h. Clofilium also extended fertilizing competence and motility of bovine-capacitated sperm, and increased the rate of fertilization with sperm capacitated for 24\u2009h by 100%, and the rate of blastocyst formation by 150%. Finally, toxicity experiments showed clofilium to have no impact on sperm DNA and no embryotoxicity at the concentration used to extend sperm lifespan. Our results demonstrate that clofilium prolongs fertilizing competence of aging capacitated sperm in vitro in both rodent and bovine species. To our knowledge, this is the first time the duration of sperm-fertilizing competence is shown to be extended by potassium channels blockers.<\/jats:p>","DOI":"10.1530\/rep-18-0075","type":"journal-article","created":{"date-parts":[[2018,11,12]],"date-time":"2018-11-12T09:37:10Z","timestamp":1542015430000},"page":"463-476","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-11","source":"Crossref","is-referenced-by-count":7,"title":["Slo3 K+ channel blocker clofilium extends bull and mouse sperm-fertilizing competence"],"prefix":"10.1093","volume":"156","author":[{"given":"Roland","family":"Abi Nahed","sequence":"first","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes , Grenoble, France"},{"name":"Institute for Advanced Biosciences INSERM U1209 , CNRS UMR5309, Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillaume","family":"Martinez","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes , Grenoble, France"},{"name":"Institute for Advanced Biosciences INSERM U1209 , CNRS UMR5309, Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean Pascal","family":"Hograindleur","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes , Grenoble, France"},{"name":"Institute for Advanced Biosciences INSERM U1209 , CNRS UMR5309, Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilie","family":"Le Bl\u00e9vec","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes , Grenoble, France"},{"name":"Institute for Advanced Biosciences INSERM U1209 , CNRS UMR5309, Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Camugli","sequence":"additional","affiliation":[{"name":"IMV Technologies , L\u2019Aigle, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Le Boucher","sequence":"additional","affiliation":[{"name":"IMV Technologies , L\u2019Aigle, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre F","family":"Ray","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes , Grenoble, France"},{"name":"Institute for Advanced Biosciences INSERM U1209 , CNRS UMR5309, Grenoble, France"},{"name":"CHU de Grenoble , UM GI-DPI, Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Escoffier","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes , Grenoble, France"},{"name":"Institute for Advanced Biosciences INSERM U1209 , CNRS UMR5309, Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Schmitt","sequence":"additional","affiliation":[{"name":"IMV Technologies , L\u2019Aigle, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christophe","family":"Arnoult","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes , Grenoble, France"},{"name":"Institute for Advanced Biosciences INSERM U1209 , CNRS UMR5309, Grenoble, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,12,1]]},"reference":[{"key":"2026010712180572400_bib1","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1002\/mrd.22871","article-title":"Reactive oxygen species as mediators of sperm capacitation and pathological damage.","volume":"84","author":"Aitken","year":"2017","journal-title":"Molecular Reproduction and Development"},{"key":"2026010712180572400_bib2","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1089\/ars.2010.3186","article-title":"Redox regulation of human sperm function: from the physiological control of sperm capacitation to the etiology of infertility and DNA damage in the germ line","volume":"14","author":"Aitken","year":"2011","journal-title":"Antioxidants and Redox Signaling"},{"key":"2026010712180572400_bib3","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1111\/rda.13115","article-title":"In vitro studies of Norwegian Red bovine semen immobilized and cryopreserved in alginate solid gel network","volume":"53","author":"Alm-Kristiansen","year":"2018","journal-title":"Reproduction in Domestic Animals"},{"key":"2026010712180572400_bib4","doi-asserted-by":"publisher","first-page":"6757","DOI":"10.1073\/pnas.96.12.6757","article-title":"Control of the low voltage-activated calcium channel of mouse sperm by egg ZP3 and by membrane hyperpolarization during capacitation","volume":"96","author":"Arnoult","year":"1999","journal-title":"PNAS"},{"key":"2026010712180572400_bib5","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/0014-5793(92)80638-W","article-title":"Effects of antiarrhythmic drugs on phospholipid metabolism in Jurkat T cells. 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