Ca2+ signalling through CatSper and Ca2+ stores regulate different behaviours in human sperm

Wardah Alasmari, Sarah Costello, Joao Correia, Senga K. Oxenham, Jennifer Morris, Leonor Fernandes, Joao Ramalho-Santos, Jackson Kirkman-Brown, Francesco Michelangeli, Stephen Publicover, Christopher L. R. Barratt

Research output: Contribution to journalArticlepeer-review

100 Citations (Scopus)
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Background: Ca2+ signals, elicited by cues from the oocyte and female tract, regulate human sperm behavior.

Results: CatSper channel activation (flagellum) and Ca2+ store mobilization (neck) caused similar [Ca2+]i elevation but induced functionally different behaviors.

Conclusion: Sperm motility pattern is determined by the site of Ca2+ mobilization.

Significance: Selection of Ca2+ signaling components and/or regulation of their availability for activation controls human sperm behavior.

[Ca2+]i signaling regulates sperm motility, enabling switching between functionally different behaviors that the sperm must employ as it ascends the female tract and fertilizes the oocyte. We report that different behaviors in human sperm are recruited according to the Ca2+ signaling pathway used. Activation of CatSper (by raising pHi or stimulating with progesterone) caused sustained [Ca2+]i elevation but did not induce hyperactivation, the whiplash-like behavior required for progression along the oviduct and penetration of the zona pellucida. In contrast, penetration into methylcellulose (mimicking penetration into cervical mucus or cumulus matrix) was enhanced by activation of CatSper. NNC55-0396, which abolishes CatSper currents in human sperm, inhibited this effect. Treatment with 5 μm thimerosal to mobilize stored Ca2+ caused sustained [Ca2+]i elevation and induced strong, sustained hyperactivation that was completely insensitive to NNC55-0396. Thimerosal had no effect on penetration into methylcellulose. 4-Aminopyridine, a powerful modulator of sperm motility, both raised pHi and mobilized Ca2+ stored in sperm (and from microsomal membrane preparations). 4-Aminopyridine-induced hyperactivation even in cells suspended in Ca2+-depleted medium and also potentiated penetration into methylcellulose. The latter effect was sensitive to NNC55-039, but induction of hyperactivation was not. We conclude that these two components of the [Ca2+]i signaling apparatus have strikingly different effects on sperm motility. Furthermore, since stored Ca2+ at the sperm neck can be mobilized by Ca2+-induced Ca2+ release, we propose that CatSper activation can elicit functionally different behaviors according to the sensitivity of the Ca2+ store, which may be regulated by capacitation and NO from the cumulus.
Original languageEnglish
Pages (from-to)6248-6258
JournalJournal of Biological Chemistry
Issue number9
Early online date23 Jan 2013
Publication statusPublished - 1 Mar 2013


  • Calcium
  • Calcium Channels
  • Calcium Intracellular Release
  • Fertilization
  • Sperm
  • CatSper
  • Hyperactivation


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