Calcium channels play a pivotal role in the sequence of ionic changes involved in initiation of mouse sperm acrosomal exocytosis.

Abstract

The sequence of ionic changes involved in initiation of acrosomal exocytosis in capacitated mouse spermatozoa was investigated. Earlier studies demonstrated that a large influx of Na+ is required for exocytosis, this Na+ apparently being associated with an increase in intracellular pH (pHi) via an Na(+)-H+ exchanger. This rise in pHi may in turn activate calcium channels and permit the influx of extracellular Ca2+ needed to trigger acrosomal exocytosis. In the present study, the dihydropyridine voltage-dependent calcium channel antagonist nifedipine was able to inhibit significantly exocytosis in sperm cells treated in various ways capable of stimulating acrosomal loss. The monovalent cation ionophore monensin can promote Na+ entry required for both capacitation and acrosomal exocytosis, as demonstrated by using chlortetracycline to monitor changes in sperm functional potential. In the presence of 10 nM nifedipine, monensin treatment accelerated capacitation but was unable to trigger exocytosis. The requirement for internalization of a high concentration of Na+ can be bypassed by the addition of 25 mM NH4Cl to raise the pHi of cells capacitated in 25 mM Na+ (insufficient Na+ to support exocytosis under usual conditions). Again, introduction of nifedipine was able to inhibit exocytosis. In a third experimental approach, amiloride-stimulated exocytosis in capacitated cells was significantly inhibited by nifedipine. In contrast to these treatments directed at specific mechanisms, the ability of the Ca2+ ionophore A23187 to promote more general entry of Ca2+ and thereby to accelerate capacitation and exocytosis was not inhibited by nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)