In the oviduct, cumulus cells that surround the oocyte release progesterone. In human sperm, progesterone stimulates a Ca 2+ increase by a non-genomic mechanism . The Ca 2+ signal has been proposed to control chemotaxis, hyperactivation and acrosomal exocytosis of sperm . However, the underlying signalling mechanism has remained mysterious. Here we show that progesterone activates the sperm-specific, pH-sensitive CatSper Ca 2+ channel . We found that both progesterone and alkaline pH stimulate a rapid Ca 2+ influx with almost no latency, incompatible with a signalling pathway involving metabotropic receptors and second messengers. The Ca 2+ signals evoked by alkaline pH and progesterone are inhibited by the Ca v channel blockers NNC 55-0396 and mibefradil. Patch-clamp recordings from sperm reveal an alkaline-activated current carried by mono- and divalent ions that exhibits all the hallmarks of sperm-specific CatSper Ca 2+ channels . Progesterone substantially enhances the CatSper current. The alkaline- and progesterone-activated CatSper current is inhibited by both drugs. Our results resolve a long-standing controversy over the non-genomic progesterone signalling. In human sperm, either the CatSper channel itself or an associated protein serves as the non-genomic progesterone receptor. The identification of CatSper channel blockers will greatly facilitate the study
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The CatSper channel mediates progesterone-induced Ca 2+ influx in human sperm
Goodwin, Normann; Brenker, Christoph; Kashikar, Nachiket D.; Weyand, Ingo; Seifert, Reinhard; Strünker, Timo; Kaupp, U. Benjamin
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, Volume 471 (7338)
Nature Publishing Group (NPG) – Mar 16, 2011
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