The Cation/Calcium Channel of Sperm (CatSper): A Common Role Played Despite Inter-Species Variation?

Abstract

The main cation/calcium channel of spermatozoa (CatSper), first identified in 2001, has been thoroughly studied to elucidate its composition and function, while its distribution among species and sperm sources is yet incomplete. CatSper is composed of several subunits that build a pore-forming calcium channel, mainly activated in vivo in ejaculated sperm cells by intracellular alkalinization and progesterone, as suggested by the in vitro examinations. The CatSper channel relevance is dual: to maintain sperm homeostasis (alongside the plethora of membrane channels present) as well as being involved in pre-fertilization events, such as sperm capacitation, hyperactivation of sperm motility and the acrosome reaction, with remarkable species differences. Interestingly, the observed variations in CatSper localization in the plasma membrane seem to depend on the source of the sperm cells explored (i.e., epididymal or ejaculated, immature or mature, processed or not), the method used for examination and, particularly, on the specificity of the antibodies employed. In addition, despite multiple findings showing the relevance of CatSper in fertilization, few studies have studied CatSper as a biomarker to fine-tune diagnosis of sub-fertility in livestock or even consider its potential to control fertilization in plague animals, a more ethically defensible strategy than implicating CatSper to pharmacologically modify male-related fertility control in humans, pets or wild animals. This review describes inter- and intra-species differences in the localization, structure and function of the CatSper channel, calling for caution when considering its potential manipulation for fertility control or improvement.

Keywords: CatSper; biomarker; calcium; livestock; sperm cells; sub-fertility.

Figure 1

Two-dimensional representation of a simplified model of the CatSper structure: 1, 2, 3 and 4 refer to the main CatSper subunits forming the calcium pore; β, γ, δ, ε, ζ and EFCAB9 refer to the accessory subunits. Protein folding and protein loops have not been considered for this model.

Figure 2

Localization of CatSper in boar sperm cells: (A) CatSper 1; (B) CatSper 2; (C) CatSper 3; (D) CatSper 4. Methodology fully described in [31], using commercially available primary antibodies anti-CatSper units (Abcam, Cambridge, UK): CatSper 1 ab101891 (diluted 1:25); CatSper 2 ab101895 (diluted 1:50); CatSper 3 ab101894 (diluted 1:50) and CatSper 4 ab101892 (diluted 1:25). Polyclonal goat anti-rabbit Alexa Fluor 568 (Molecular Probes, Invitrogen, Carlsbad, CA, USA), was used as secondary antibody, diluted 1:1000. The samples were examined under a LSM 700 Zeiss confocal microscope (Carl Zeiss, Sweden) at 630× using DIC and images recorded using ZEN Navigator software (Carl Zeiss, Sweden).

Figure 3

Intracellular pathways and sperm outcome after intracellular alkalinization due to bicarbonate entrance in sperm cells (gray), activation of CatSper channel (pink), the opioid receptors (blue) and potassium channels (purple). Green lines indicate stimulation or activation, and red lines blockade or inhibition. Modified from [3].