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CatSper controls the intracellular Ca<jats:sup>2+<\/jats:sup> concentration and, thereby, the motility of human sperm. Activation of CatSper by oviductal ligands evokes a transient Ca<jats:sup>2+<\/jats:sup> increase, which entails changes in the flagellar beat that are required for fertilisation. The CatSper\u2010mediated Ca<jats:sup>2+<\/jats:sup> influx has been studied extensively, whereas the mechanisms underlying Ca<jats:sup>2+<\/jats:sup> clearance and recovery from Ca<jats:sup>2+<\/jats:sup> influx have remained ill\u2010defined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We examined how pharmacological suppression of Ca<jats:sup>2+<\/jats:sup> export from the cytosol into the extracellular space or Ca<jats:sup>2+<\/jats:sup> uptake into intracellular stores affects the resting Ca<jats:sup>2+<\/jats:sup> concentration and CatSper\u2010mediated Ca<jats:sup>2+<\/jats:sup> signals in human sperm. We studied sperm of healthy volunteers and infertile men lacking functional CatSper channels, using kinetic Ca<jats:sup>2+<\/jats:sup>\u2010 and pH\u2010fluorometry as well as patch\u2010clamp recordings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>We show that Ca<jats:sup>2+<\/jats:sup> entering human sperm via CatSper is predominantly, if not exclusively, exported by plasma membrane Ca<jats:sup>2+<\/jats:sup> ATPases (PMCAs). Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup> exchange and Ca<jats:sup>2+<\/jats:sup> uptake into intracellular stores or mitochondria play no or only a negligible role in Ca<jats:sup>2+<\/jats:sup> clearance in human sperm.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Ca<jats:sup>2+<\/jats:sup> signalling in human sperm is controlled by the functional interplay of CatSper and PMCAs, that is, the balance between Ca<jats:sup>2+<\/jats:sup> influx and Ca<jats:sup>2+<\/jats:sup> export that is required for human sperm function and fertilisation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.70009","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T11:44:16Z","timestamp":1741088656000},"page":"2694-2712","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Chemosensory signalling in human sperm is controlled by Ca<sup>2+<\/sup> influx via CatSper and Ca<sup>2+<\/sup> clearance via plasma membrane Ca<sup>2+<\/sup> ATPases"],"prefix":"10.1111","volume":"182","author":[{"given":"Leonie","family":"Herrmann","sequence":"first","affiliation":[{"name":"Centre of Reproductive Medicine and Andrology, University Hospital M\u00fcnster University of M\u00fcnster  M\u00fcnster Germany"},{"name":"Centre of Medical Genetics, Institute of Reproductive Genetics University of M\u00fcnster  M\u00fcnster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Brenker","sequence":"additional","affiliation":[{"name":"Centre of Reproductive Medicine and Andrology, University Hospital M\u00fcnster University of M\u00fcnster  M\u00fcnster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Mittermair","sequence":"additional","affiliation":[{"name":"Centre of Reproductive Medicine and Andrology, University Hospital M\u00fcnster University of M\u00fcnster  M\u00fcnster Germany"},{"name":"GRK 2515, Chemical Biology of Ion Channels (Chembion) University of M\u00fcnster  M\u00fcnster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vesna","family":"Bojovic","sequence":"additional","affiliation":[{"name":"Centre of Reproductive Medicine and Andrology, University Hospital M\u00fcnster University of M\u00fcnster  M\u00fcnster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"M\u00fcnchow","sequence":"additional","affiliation":[{"name":"GRK 2515, Chemical Biology of Ion Channels (Chembion) University of M\u00fcnster  M\u00fcnster Germany"},{"name":"Institute of Pharmaceutical and Medicinal Chemistry, Pharmacampus University of M\u00fcnster  M\u00fcnster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. 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