STUDIES OF PORCINE AND HUMAN SPERM SUGGESTING A ROLE FOR A SPERM GLYCINE RECEPTOR CL- CHANNEL IN THE ZONA PELLUCIDA-INITIATED ACROSOME REACTION

It is known that Cl- is required for the zona pellucida (zona)- and pr ogesterone-initiated mammalian sperm acrosome reaction (AR). Recent ev idence indicates the involvement of a unique progesterone receptor res embling a GABA(A) receptor/Cl- channel in the latter event. in the stu dy reported here, we investigated whether the in vitro porcine sperm A R initiated by heat-solubilized porcine zonae involves a different rec eptor/Cl- channel than does the progesterone-initiated AR. Capacitated porcine sperm failed to undergo the zona- and progesterone-initiated AR when suspended in a medium deficient in Cl-. We then employed 1) st rychnine, an antagonist of neuronal glycine receptor/Cl- channels at n anomolar concentrations and of GABA(A) receptor/Cl- channels at microm olar concentrations and 2) (+)-bicuculline, an antagonist of neuronal GABA(A) receptor/Cl- channels that inhibits glycine receptor/Cl- chann els only at higher concentrations. We report here that the zona-initia ted AR was inhibited by 50 nM strychnine, but the progesterone-initiat ed AR required 1 mu M for inhibition. Moreover, 1 mu M (+)-bicuculline inhibited the progesterone-initiated AR, but the zona-initiated AR re quired 50 mu M for inhibition. In addition, glycine initiated the porc ine sperm AR, and that event was inhibited by strychnine acid (+)-bicu culline with the same order of potency observed for the zona-initiated AR. Finally, glycine initiated the AR in human sperm, and that initia tion was inhibited by 50 nM strychnine. This work provides the first e vidence suggesting that a glycine receptor/Cl- channel is involved in the zona-initiated mammalian sperm AR.