A caged progesterone analog alters intracellular Ca2+ and flagellar bending in human sperm

Servin‐Vences, M. Rocio; Tatsu, Yoshiro; Ando, Hisanori; Guerrero, Adán; Yumoto, Noboru; Darszon, Alberto; Nishigaki, Takuya

doi:10.1530/rep-11-0268

Cited by 32 publications

(27 citation statements)

References 43 publications

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“…Consistent with recent reports that progesterone directly activates CatSper channels [11,12], the [Ca 2+ ] i response in the anterior principal piece preceded that in the PHN region by 1.6±0.2 s ( n =29 cells; P <10 −8 ) (Figure 5f). A similar spatio-temporal pattern has recently been reported upon photolysis of caged progesterone [45]. When a sustained [Ca 2+ ] i increase occurred in the midpiece there was often a clear inflexion in the rising phase after 10–30 s (Figures 5f and 5g; Supplementary Movies S1 and S2 at http://www.BiochemJ.org/bj/448/bj4480189add.htm).…”

Section: Resultssupporting

confidence: 80%

2-APB-potentiated channels amplify CatSper-induced Ca2+ signals in human sperm

Lefièvre

Nash

Mansell

et al. 2012

Biochemical Journal

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Ca2+i signalling is pivotal to sperm function. Progesterone, the best-characterized agonist of human sperm Ca2+i signalling, stimulates a biphasic [Ca2+]i rise, comprising a transient and subsequent sustained phase. In accordance with recent reports that progesterone directly activates CatSper, the [Ca2+]i transient was detectable in the anterior flagellum (where CatSper is expressed) 1–2 s before responses in the head and neck. Pre-treatment with 5 μM 2-APB (2-aminoethoxydiphenyl borate), which enhances activity of store-operated channel proteins (Orai) by facilitating interaction with their activator [STIM (stromal interaction molecule)] ‘amplified’ progesterone-induced [Ca2+]i transients at the sperm neck/midpiece without modifying kinetics. The flagellar [Ca2+]i response was unchanged. 2-APB (5 μM) also enhanced the sustained response in the midpiece, possibly reflecting mitochondrial Ca2+ accumulation downstream of the potentiated [Ca2+]i transient. Pre-treatment with 50–100 μM 2-APB failed to potentiate the transient and suppressed sustained [Ca2+]i elevation. When applied during the [Ca2+]i plateau, 50–100 μM 2-APB caused a transient fall in [Ca2+]i, which then recovered despite the continued presence of 2-APB. Loperamide (a chemically different store-operated channel agonist) enhanced the progesterone-induced [Ca2+]i signal and potentiated progesterone-induced hyperactivated motility. Neither 2-APB nor loperamide raised pHi (which would activate CatSper) and both compounds inhibited CatSper currents. STIM and Orai were detected and localized primarily to the neck/midpiece and acrosome where Ca2+ stores are present and the effects of 2-APB are focussed, but store-operated currents could not be detected in human sperm. We propose that 2-APB-sensitive channels amplify [Ca2+]i elevation induced by progesterone (and other CatSper agonists), amplifying, propagating and providing spatio-temporal complexity in [Ca2+]i signals of human sperm.

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Section: Resultssupporting

confidence: 80%

2-APB-potentiated channels amplify CatSper-induced Ca2+ signals in human sperm

Lefièvre

Nash

Mansell

et al. 2012

Biochemical Journal

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“…CatSper and Slo3 are both located in the principal piece. Moreover, progesterone-induced Ca 2+ signals originate in the flagellum and propagate in a tail-to-head direction (Servin-Vences et al, 2012). Due to the miniscule flagellar volume (about 2.5 fl), opening a few CatSper channels, each conducting several thousand Ca 2+ ions per second, would increase local flagellar [Ca 2+ ] to levels that should readily exceed global [Ca 2+ ] i .…”

Section: Discussionmentioning

confidence: 99%

The Ca2+-activated K+ current of human sperm is mediated by Slo3

Brenker

Zhou

Müller

et al. 2014

eLife

157

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Sperm are equipped with a unique set of ion channels that orchestrate fertilization. In mouse sperm, the principal K+ current (IKSper) is carried by the Slo3 channel, which sets the membrane potential (Vm) in a strongly pHi-dependent manner. Here, we show that IKSper in human sperm is activated weakly by pHi and more strongly by Ca2+. Correspondingly, Vm is strongly regulated by Ca2+ and less so by pHi. We find that inhibitors of Slo3 suppress human IKSper, and we identify the Slo3 protein in the flagellum of human sperm. Moreover, heterologously expressed human Slo3, but not mouse Slo3, is activated by Ca2+ rather than by alkaline pHi; current–voltage relations of human Slo3 and human IKSper are similar. We conclude that Slo3 represents the principal K+ channel in human sperm that carries the Ca2+-activated IKSper current. We propose that, in human sperm, the progesterone-evoked Ca2+ influx carried by voltage-gated CatSper channels is limited by Ca2+-controlled hyperpolarization via Slo3.DOI: http://dx.doi.org/10.7554/eLife.01438.001

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“…In many species, the acrosome reaction is initiated by the glycoproteins of the zona pellucida 23,24 and can be accelerated by progesterone. [25][26][27] …”

Section: The Spermmentioning

confidence: 99%