Sequential focal and global elevations of sperm intracellular Ca2+ are initiated by the zona pellucida during acrosomal exocytosis.

The acrosome reaction is a Cai(2+)-dependent secretory event that is initiated in mammalian sperm by ZP3, the stimulatory agonist in the egg's zona pellucida. Video image processing-enhanced fluorescence microscopy was used to monitor sperm Cai2+ responses to agonist during exocytosis. Two types of agonist-dependent Cai2+ transport pathways were defined. The first mediates small, transient Cai2+ elevations that are restricted to the sperm head. Dye emission and quenching studies indicate that this focal channel is not voltage-regulated, conducts several divalent metal cations (Co2+, Mn2+, and Ni2+) in addition to Ca2+, and has the properties of a poorly selective cation channel. The second transporter mediates sustained Cai2+ elevations throughout the cell and is pharmacologically identical to the L-type of voltage-sensitive Ca2+ channel. These channels are distinguished by inhibitor sensitivity and by their regulation during sperm maturation. A model is proposed in which ZP3 initiates a G protein-independent opening of the cation channel, producing depolarization of sperm membrane potential and consequent opening of L channels. The coordinate regulation of sperm Ca2+ channels by ZP3 during gamete adhesion promotes acrosomal exocytosis.