KSper, a pH-sensitive K⁺ current that controls sperm membrane potential

Mature mammalian spermatozoa are quiescent in the male reproductive tract. Upon ejaculation and during their transit through the female reproductive tract, they undergo changes that enable them to fertilize the egg. During this process of capacitation, they acquire progressive motility, develop hyperactivated motility, and are readied for the acrosome reaction. All of these processes are regulated by intracellular pH. In the female reproductive tract, the spermatozoan cytoplasm alkalinizes, which in turn activates a Ca ²⁺-selective current (I_CatSper) required for hyperactivated motility. Here, we show that alkalinization also has a dramatic effect on membrane potential, producing a rapid hyperpolarization. This hyperpolarization is primarily mediated by a weakly outwardly rectifying K ⁺ current (I_KSper) originating from the principal piece of the sperm flagellum. Alkalinization activates the pH_i-sensitive I_KSper, setting the membrane potential to negative potentials where Ca²⁺ entry via I_CatSper is maximized. I_KSper is one of two dominant ion currents of capacitated sperm cells.