title: The Ca2+-activated K+ current of human sperm is mediated by Slo3.
abstract: Sperm are equipped with a unique set of ion channels that orchestrate fertilization. In mouse sperm, the principal K(+) current (IKSper) is carried by the Slo3 channel, which sets the membrane potential (Vm) in a strongly pHi-dependent manner. Here, we show that IKSper in human sperm is activated weakly by pHi and more strongly by Ca(2+). Correspondingly, Vm is strongly regulated by Ca(2+) and less so by pHi. We find that inhibitors of Slo3 suppress human IKSper, 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 pHi; current-voltage relations of human Slo3 and human IKSper are similar. We conclude that Slo3 represents the principal K(+) channel in human sperm that carries the Ca(2+)-activated IKSper 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.
authors.affiliation: Department of Molecular Sensory Systems, Center of Advanced European Studies and Research, Bonn, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Brenker
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Astrid
authors.initials: A
authors.lastname: Müller
authors.forename: Fabio Andres
authors.initials: FA
authors.lastname: Echeverry
authors.forename: Christian
authors.initials: C
authors.lastname: Trötschel
authors.forename: Ansgar
authors.initials: A
authors.lastname: Poetsch
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Xia
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bönigk
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Lingle
authors.forename: U Benjamin
authors.initials: UB
authors.lastname: Kaupp
authors.forename: Timo
authors.initials: T
authors.lastname: Strünker
mesh_terms: D002118:Calcium / Q000378:metabolism*; D005407:Flagella / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D011188:Potassium / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism*; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*
chemical_list: C577767:KCNU1 protein, human; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011188:Potassium; D002118:Calcium
keywords: Ca2+-activated K+ channel; Slo3; human sperm; ion channels; patch-clamp recordings