Figure 12. Role of human KSper (Slo1) in sperm physiology.
In the uterus and fallopian tube, CatSper is partially activated due to the intracellular alkalinization evoked by proton extrusion through Hv1 and picomolar- to nanomolar progesterone (P) concentrations. However, to achieve full activation of CatSper, flagellar plasma membrane must be depolarized. This is achieved by the inhibition of sperm KSper, the channel responsible for membrane hyperpolarization. In close proximity to the oocyte, spermatozoa encounter micromolar concentrations of P, which inhibit hKSper, resulting in membrane depolarization. These events allow full activation of CatSper, trigger sperm hyperactivation, allow spermatozoa to penetrate through the egg protective vestment, and make fertilization possible.