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Its sensitivity to both voltage and alkalization plays a crucial role in sperm fertility, which is tightly coupled to the capacitation process. Here, we show that sperm-enriched divalent cation Zn\n                    <jats:sup>2+<\/jats:sup>\n                    undergoes dynamic alteration in spermatozoa during capacitation. We also found that intracellular Zn\n                    <jats:sup>2+<\/jats:sup>\n                    regulates alkalinization-induced hyperpolarization in mouse spermatozoa, which is mediated by the Slo3 channel. Further examination of zinc regulation in mouse Slo3 (mSlo3) revealed that, in the\n                    <jats:italic>Xenopus<\/jats:italic>\n                    oocyte expression system\n                    <jats:italic>,<\/jats:italic>\n                    intracellular zinc directly inhibits mouse Slo3 currents in a dose-dependent manner at micromolar concentrations, with exceptionally slow dissociation. By combining MD simulations and electrophysiology, we also identified amino acid residues contributing to the Zn\n                    <jats:sup>2+<\/jats:sup>\n                    slow dissociation from Slo3 channels. Our studies uncover the importance of intracellular zinc dynamics and its regulatory role in ion channels during sperm capacitation.\n                  <\/jats:p>","DOI":"10.7554\/elife.105450","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T12:44:25Z","timestamp":1743597865000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.105450","source":"Crossref","is-referenced-by-count":0,"title":["Zinc is a key regulator of the sperm-specific K+ channel (Slo3) function"],"prefix":"10.7554","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9242-469X","authenticated-orcid":true,"given":"Rizki Tsari","family":"Andriani","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/035t8zc32","id-type":"ROR","asserted-by":"publisher"}],"name":"Integrative Physiology, Graduate School of Medicine, The University of Osaka","place":["Suita, 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