The Ca(2+)-activated K(+) current of human sperm is mediated by Slo3

Sperm are equipped with a unique set of ion channels that orchestrate fertilization. In mouse sperm, the principal K(+) current (I(KSper)) is carried by the Slo3 channel, which sets the membrane potential (V(m)) in a strongly pH(i)-dependent manner. Here, we show that I(KSper) in human sperm is activated weakly by pH(i) and more strongly by Ca(2+). Correspondingly, V(m) is strongly regulated by Ca(2+) and less so by pH(i). We find that inhibitors of Slo3 suppress human I(KSper), and we identify the Slo3 protein in the flagellum of human sperm. Moreover, heterologously expressed human Slo3, but not mouse Slo3, is activated by Ca(2+) rather than by alkaline pH(i); current–voltage relations of human Slo3 and human I(KSper) are similar. We conclude that Slo3 represents the principal K(+) channel in human sperm that carries the Ca(2+)-activated I(KSper) current. We propose that, in human sperm, the progesterone-evoked Ca(2+) influx carried by voltage-gated CatSper channels is limited by Ca(2+)-controlled hyperpolarization via Slo3. DOI: http://dx.doi.org/10.7554/eLife.01438.001