Prof. Dr. U. Benjamin Kaupp
center of advanced european studies and research (caesar)
u.b.kaupp@caesar.de View member: Prof. Dr. U. Benjamin Kaupp
British journal of pharmacology
BACKGROUND AND PURPOSE: Loss of function of the sperm-specific Ca channel CatSper is a common channelopathy that causes male infertility. CatSper controls the intracellular Ca concentration and, thereby, the motility of human sperm. Activation of CatSper by oviductal ligands evokes a transient Ca increase, which entails changes in the flagellar beat that are required for fertilisation. The CatSper-mediated Ca influx has been studied extensively, whereas the mechanisms underlying Ca clearance and recovery from Ca influx have remained ill-defined.
EXPERIMENTAL APPROACH: We examined how pharmacological suppression of Ca export from the cytosol into the extracellular space or Ca uptake into intracellular stores affects the resting Ca concentration and CatSper-mediated Ca signals in human sperm. We studied sperm of healthy volunteers and infertile men lacking functional CatSper channels, using kinetic Ca- and pH-fluorometry as well as patch-clamp recordings.
KEY RESULTS: We show that Ca entering human sperm via CatSper is predominantly, if not exclusively, exported by plasma membrane Ca ATPases (PMCAs). Na/Ca exchange and Ca uptake into intracellular stores or mitochondria play no or only a negligible role in Ca clearance in human sperm.
CONCLUSIONS AND IMPLICATIONS: Ca signalling in human sperm is controlled by the functional interplay of CatSper and PMCAs, that is, the balance between Ca influx and Ca export that is required for human sperm function and fertilisation.
© 2025 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
PMID: 40016153