Ion fluxes through the progesterone-activated channel of the sperm plasma membrane.

We have characterized ionic changes triggered by progesterone in human spermatozoa. This steroid, which is a fast-acting stimulator of the acrosome reaction, triggered a rapid increase in the cytoplasmic Ca2+ concentration ([Ca2+]i) which was entirely due to influx across the plasma membrane, as it was obliterated by chelation of extracellular Ca2+. Ca2+ fluxes were insensitive to verapamil and pertussis toxin, thus suggesting that they did not occur via voltage-gated channels and did not involve a pertussis toxin-sensitive G protein, and were potentiated in Na(+)-free, choline-containing or methylglucamine-containing medium. Progesterone also caused a depolarization of the plasma membrane in Na(+)-containing as well as in choline- or methyl-glucamine-containing saline; depolarization was larger in the absence of extracellular Ca2+, suggesting that Na+ and Ca2+ fluxes occurred through the same channel. Progesterone was able to trigger the acrosome reaction in the three media investigated (Na+, choline and methylglucamine), provided that extracellular Ca2+ was also present. We conclude that progesterone activates a membrane ion channel that is permeable to monovalent cations as well as to Ca2+.