ACTIVATION OF MOUSE SPERM T-TYPE CA2-PELLUCIDA( CHANNELS BY ADHESION TO THE EGG ZONA)

The sperm acrosome reaction is a Ca2+-dependent exocytotic event that is triggered by adhesion to the mammalian egg's zona pellucida. Previo us studies using ion-selective fluorescent probes suggested a role of voltage-sensitive Ca2+ channels in acrosome reactions. Here, whole-cel l patch clamp techniques are used to demonstrate the expression of fun ctional T-type Ca2+ channels during mouse spermatogenesis, The germ ce ll T current is inhibited hy antagonists of T-type channels (pimozide and amiloride) as well as by antagonists whose major site of action is the somatic cell L-type Ca2+ channel (1,4-dihydropyridines, arylalkyl amines, benzothiazapines), as has also been reported for certain somat ic cell T currents. In sperm, inhibition of T channels during gamete i nteraction inhibits zona pellucida-dependent Ca2+ elevations, as demon strated by ion-selective fluorescent probes, and also inhibits acrosom e reactions. These studies directly link sperm T-type Ca2+ channels to fertilization, In addition, the kinetics of channel inhibition by 1,4 -dihydropyridines suggests a mechanism for the reported contraceptive effects of those compounds in human males.