Figure 1.

(A) The upper panel shows the ‘classical’ model for agonist-induced Ca²⁺ influx in human sperm incorporating action of odorants and other agonists via trans-membrane adenyl cyclase (tmAC). Various receptors, represented by different colours, are each activated by discrete agonists. Generation of cAMP leads to activation of Ca²⁺-permeable channels (grey). CatSper (purple) is probably restricted to the flagellum (see B) and is regulated by progesterone, prostaglandins, pH_i and (weakly) V_m. Other ionotropic and metabotropic receptors have also been described in sperm but are not shown. The lower panel shows a model based upon the conclusions of Brenker et al in which the tmAC and the regulation of Ca²⁺-permeable channels by cAMP are ‘greyed out’. CatSper acts as a ‘polymodal sensor for chemical cues’ as well as responding to pH_i and V_m. (B) Restriction of CatSper (purple) to the membrane of the flagellar principal piece (as occurs in mouse sperm) will result in all CatSper-mediated [Ca²⁺]_i signals originating here. Though rapid diffusion will occur there is apparently limited scope for flexibility of responses elicited by the various stimuli that converge on CatSper. This could be provided by Ca²⁺ storage organelles in the head and neck (yellow). (C) Propagation of Ca²⁺ signals into the sperm neck and head by Ca²⁺-induced release of stored Ca²⁺ (CICR) and activation of store operated channels (SOCs) may be regulated by cues from the female tract and/or by processes occurring during sperm capacitation such as oxidative stress and activation of kinases and phosphatases (lower panel), such that the spatio-temporal characteristics of the signal generated by activation of CatSper depends on the ‘readiness’ of the cell.