Induction of Accelerated Acrosome Reaction in Guinea Pig Sperm1

Abstract
Methoxyverapamil (D600) usually described as an antagonist of Ca2+ transport, has unexpected effects upon guinea pig spermatozoa. Optimal concentrations (50–150 µM) of D600 accelerate the acrosome reaction and the release of the acrosomal enzyme, hyaluronidase, during capacitation in vitro. These actions of the drug require the presence of extracellular Ca2+ and are preceded by enhanced uptake of 45Ca2+ into the sperm. Using the relatively synchronous capacitation system described here, we have found that high concentrations of Ca2+ exert an adverse effect on the survival of spermatozoa that have undergone acrosome reaction. The deleterious effects can be prevented in part by addition of the mitochondrial Ca2+ uptake inhibitor, ruthenium red, or by chelation of Ca2+ after the acrosome reaction has occurred. These results suggest that, although uptake of Ca2+ by sperm is required for the acrosome reaction, additional mechanisms may operate to protect the sperm by limiting the entry of Ca2+ during capacitation in vivo.