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

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, Strünker

Abstract

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.