Brenker Christoph, Zhou Yu, Müller Astrid, Echeverry Fabio Andres, Trötschel Christian, Poetsch Ansgar, Xia Xiao-Ming, Bönigk Wolfgang, Lingle Christopher J, Kaupp U Benjamin, Strünker Timo
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research, Bonn, Germany.
Elife. 2014 Mar 26;3:e01438. doi: 10.7554/eLife.01438.
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.
精子配备有一组独特的离子通道，这些通道协调受精过程。在小鼠精子中，主要的钾离子电流（IKSper）由Slo3通道携带，该通道以强烈依赖细胞内pH值（pHi）的方式设定膜电位（Vm）。在此，我们表明人类精子中的IKSper受pHi的微弱激活，而受钙离子（Ca(2+)）的强烈激活。相应地，Vm受Ca(2+)的强烈调节，而受pHi的调节较弱。我们发现Slo3抑制剂可抑制人类IKSper，并且我们在人类精子鞭毛中鉴定出了Slo3蛋白。此外，异源表达的人类Slo3而非小鼠Slo3受Ca(2+)而非碱性pHi的激活；人类Slo3和人类IKSper的电流-电压关系相似。我们得出结论，Slo3代表人类精子中携带Ca(2+)激活的IKSper电流的主要钾离子通道。我们提出，在人类精子中，电压门控的CatSper通道所携带的孕酮诱发的Ca(2+)内流受Slo3介导的Ca(2+)控制的超极化作用限制。DOI: http://dx.doi.org/10.7554/eLife.01438.001 。
