Acrosomal alkalization triggers Ca2+ release and acrosome reaction in mammalian spermatozoa

作者：Chavez Julio C; De la Vega Beltran Jose L; Jose Omar; Torres Paulina; Nishigaki Takuya; Trevino Claudia L; Darszon Alberto

来源：Journal of Cellular Physiology, 2018, 233(6): 4735-4747.

DOI：10.1002/jcp.26262

<jats:sec><jats:label /><jats:p>The sperm acrosome reaction (AR), an essential event for mammalian fertilization, involves Ca<jats:sup>2+</jats:sup> permeability changes leading to exocytosis of the acrosomal vesicle. The acrosome, an intracellular Ca<jats:sup>2+</jats:sup> store whose luminal pH is acidic, contains hydrolytic enzymes. It is known that acrosomal pH (pH<jats:sub>acr</jats:sub>) increases during capacitation and this correlates with spontaneous AR. Some AR inducers increase intracellular Ca<jats:sup>2+</jats:sup> concentration ([Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>) through Ca<jats:sup>2+</jats:sup> release from internal stores, mainly the acrosome. Catsper, a sperm specific Ca<jats:sup>2+</jats:sup> channel, has been suggested to participate in the AR. Curiously, Mibefradil and NNC55‐0396, two CatSper blockers, themselves elevate [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> by unknown mechanisms. Here we show that these compounds, as other weak bases, can elevate pH<jats:sub>acr</jats:sub>, trigger Ca<jats:sup>2+</jats:sup> release from the acrosome, and induce the AR in both mouse and human sperm. To our surprise, μM concentrations of NNC55‐0396 induced AR even in nominally Ca<jats:sup>2+</jats:sup> free media. Our findings suggest that alkalization of the acrosome is critical step for Ca<jats:sup>2+</jats:sup> release from the acrosome that leads to the acrosome reaction.</jats:p></jats:sec>

• 出版日期2018-6