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The acrosome, an intracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      store whose luminal pH is acidic, contains hydrolytic enzymes. It is known that acrosomal pH (pH\n                      <jats:sub>acr<\/jats:sub>\n                      ) increases during capacitation and this correlates with spontaneous AR. Some AR inducers increase intracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      concentration ([Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ]\n                      <jats:sub>i<\/jats:sub>\n                      ) through Ca\n                      <jats:sup>2+<\/jats:sup>\n                      release from internal stores, mainly the acrosome. Catsper, a sperm specific Ca\n                      <jats:sup>2+<\/jats:sup>\n                      channel, has been suggested to participate in the AR. Curiously, Mibefradil and NNC55\u20100396, two CatSper blockers, themselves elevate [Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ]\n                      <jats:sub>i<\/jats:sub>\n                      by unknown mechanisms. Here we show that these compounds, as other weak bases, can elevate pH\n                      <jats:sub>acr<\/jats:sub>\n                      , trigger Ca\n                      <jats:sup>2+<\/jats:sup>\n                      release from the acrosome, and induce the AR in both mouse and human sperm. To our surprise, \u03bcM concentrations of NNC55\u20100396 induced AR even in nominally Ca\n                      <jats:sup>2+<\/jats:sup>\n                      free media. Our findings suggest that alkalization of the acrosome is critical step for Ca\n                      <jats:sup>2+<\/jats:sup>\n                      release from the acrosome that leads to the acrosome reaction.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcp.26262","type":"journal-article","created":{"date-parts":[[2017,11,14]],"date-time":"2017-11-14T08:26:44Z","timestamp":1510648004000},"page":"4735-4747","source":"Crossref","is-referenced-by-count":48,"title":["Acrosomal alkalization triggers Ca\n                    <sup>2+<\/sup>\n                    release and acrosome reaction in mammalian spermatozoa"],"prefix":"10.1002","volume":"233","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7375-9531","authenticated-orcid":false,"given":"Julio C.","family":"Ch\u00e1vez","sequence":"first","affiliation":[{"name":"Departamento de Gen\u00e9tica del Desarrollo y Fisiolog\u00eda Molecular Instituto de Biotecnolog\u00eda Universidad Nacional Aut\u00f3noma de M\u00e9xico Cuernavaca, Morelos, CP M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 L.","family":"De la Vega\u2010Beltr\u00e1n","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica del Desarrollo y Fisiolog\u00eda Molecular Instituto de Biotecnolog\u00eda Universidad Nacional Aut\u00f3noma de M\u00e9xico Cuernavaca, Morelos, CP M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Jos\u00e9","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica del Desarrollo y Fisiolog\u00eda Molecular Instituto de Biotecnolog\u00eda Universidad Nacional Aut\u00f3noma de M\u00e9xico Cuernavaca, Morelos, CP M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Torres","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica del Desarrollo y Fisiolog\u00eda Molecular Instituto de Biotecnolog\u00eda Universidad Nacional Aut\u00f3noma de M\u00e9xico Cuernavaca, Morelos, CP M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Nishigaki","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica del Desarrollo y Fisiolog\u00eda Molecular Instituto de Biotecnolog\u00eda Universidad Nacional Aut\u00f3noma de M\u00e9xico Cuernavaca, Morelos, CP M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia L.","family":"Trevi\u00f1o","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica del Desarrollo y Fisiolog\u00eda Molecular Instituto de Biotecnolog\u00eda Universidad Nacional Aut\u00f3noma de M\u00e9xico Cuernavaca, Morelos, CP M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Darszon","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica del Desarrollo y Fisiolog\u00eda Molecular Instituto de Biotecnolog\u00eda Universidad Nacional Aut\u00f3noma de M\u00e9xico Cuernavaca, Morelos, CP M\u00e9xico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.439356"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e13-09-0523"},{"issue":"2009","key":"e_1_2_8_4_1","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1095\/biolreprod.109.080127","article-title":"Human sperm thermotaxis is mediated by phospholipase C and inositol trisphosphate receptor Ca2+ channel","volume":"82","author":"Bahat A.","year":"2010","journal-title":"Biology of Reproduction"},{"issue":"8","key":"e_1_2_8_5_1","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0076-6879(08)04007-X","article-title":"Live\u2010cell imaging of autophagy induction and autophagosome\u2010 lysosome fusion in primary cultured neurons","volume":"453","author":"Bains M.","year":"2009","journal-title":"Methods in Enzymology"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2009.02.061"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2016.10.002"},{"key":"e_1_2_8_8_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/978-3-319-30567-7_3","volume-title":"Sperm acrosome biogenesis and function during fertilization","author":"Beltr\u00e1n C.","year":"2016"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0143-4160(93)90018-2"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2012.30"},{"issue":"5","key":"e_1_2_8_11_1","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1387\/ijdb.072532mb","article-title":"The role of the acrosomal matrix in fertilization","volume":"52","author":"Buffone M. 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