Figure 1. Proton regulation and CatSper function in mouse versus human spermatozoa.

In mouse spermatozoa, intracellular alkalinisation is achieved via activity of Na⁺-dependent (Cl⁻/HCO₃⁻) exchanger (NCB) and sperm-specific Na⁺/H⁺ exchanger (sNHE). NCB also helps to accumulate bicarbonate ions (HCO₃⁻) to stimulate bicarbonate-dependent atypical adenylyl cyclase (ADCY10), which leads to elevation of intracellular cAMP (Hess et al. 2005; Carlson et al. 2007) and possible stimulation of sNHE, which has a cAMP binding site (Wang et al. 2003). In human spermatozoa, the voltage-gated proton channel Hv1 is likely to constitute the main proton extrusion mechanism. Activation of Hv1 by anandamide (AEA), removal of extracellular zinc, and the alkaline environment of the female reproductive tract cause intracellular alkalisation. In both mouse and human sperm cells, intracellular alkalinisation activates the calcium channel CatSper that allows calcium ions to enter sperm flagellum. The rise in intracellular calcium causes hyperactivation and prepares spermatozoa to undergo the acrosome reaction.