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British journal of pharmacology · 2025

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

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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

Аннотация

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.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты