Chemosensory signalling in human sperm is controlled by Ca2+ influx via CatSper and Ca2+ clearance via plasma membrane Ca2+ ATPases

• Published in: British journal of pharmacology Vol. 182; no. 12; pp. 2694 - 2712
• Main Authors: Herrmann, Leonie, Brenker, Christoph, Mittermair, Teresa, Bojovic, Vesna, Münchow, Jens, Zhu, W. Felix, Trugge, Carla, Fußhöller, David, Jikeli, Jan, Temme, Louisa, Kaupp, U. Benjamin, Strünker, Timo
• Format: Journal Article
• Language: English
• Published: 01.06.2025
• Subjects: Ca2+ signaling; CatSper; human sperm; PMCA
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/bph.70009

Background and Purpose Loss of function of the sperm‐specific Ca2+ channel CatSper is a common channelopathy that causes male infertility. CatSper controls the intracellular Ca2+ concentration and, thereby, the motility of human sperm. Activation of CatSper by oviductal ligands evokes a transient Ca2+ increase, which entails changes in the flagellar beat that are required for fertilisation. The CatSper‐mediated Ca2+ influx has been studied extensively, whereas the mechanisms underlying Ca2+ clearance and recovery from Ca2+ influx have remained ill‐defined. Experimental Approach We examined how pharmacological suppression of Ca2+ export from the cytosol into the extracellular space or Ca2+ uptake into intracellular stores affects the resting Ca2+ concentration and CatSper‐mediated Ca2+ signals in human sperm. We studied sperm of healthy volunteers and infertile men lacking functional CatSper channels, using kinetic Ca2+‐ and pH‐fluorometry as well as patch‐clamp recordings. Key Results We show that Ca2+ entering human sperm via CatSper is predominantly, if not exclusively, exported by plasma membrane Ca2+ ATPases (PMCAs). Na+/Ca2+ exchange and Ca2+ uptake into intracellular stores or mitochondria play no or only a negligible role in Ca2+ clearance in human sperm. Conclusions and Implications Ca2+ signalling in human sperm is controlled by the functional interplay of CatSper and PMCAs, that is, the balance between Ca2+ influx and Ca2+ export that is required for human sperm function and fertilisation.