Activation of mouse sperm T-type Ca2+ channels by adhesion to the egg zona pellucida

Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13004-9. doi: 10.1073/pnas.93.23.13004.

Abstract

The sperm acrosome reaction is a Ca(2+)-dependent exocytotic event that is triggered by adhesion to the mammalian egg's zona pellucida. Previous studies using ion-selective fluorescent probes suggested a role of voltage-sensitive Ca2+ channels in acrosome reactions. Here, wholecell patch clamp techniques are used to demonstrate the expression of functional T-type Ca2+ channels during mouse spermatogenesis. The germ cell T current is inhibited by 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, arylalkylamines, benzothiazapines), as has also been reported for certain somatic cell T currents. In sperm, inhibition of T channels during gamete interaction inhibits zona pellucida-dependent Ca2+ elevations, as demonstrated by ion-selective fluorescent probes, and also inhibits acrosome 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acrosome / drug effects
  • Acrosome / physiology
  • Amiloride / pharmacology
  • Animals
  • Calcium / metabolism
  • Calcium Channels / drug effects
  • Calcium Channels / physiology*
  • Contraceptive Agents, Male
  • Dihydropyridines / pharmacology*
  • Female
  • Humans
  • Kinetics
  • Male
  • Membrane Potentials / drug effects
  • Mice
  • Pimozide / pharmacology
  • Sperm-Ovum Interactions*
  • Spermatozoa / physiology*
  • Testis / physiology
  • Zona Pellucida / physiology*

Substances

  • Calcium Channels
  • Contraceptive Agents, Male
  • Dihydropyridines
  • Pimozide
  • Amiloride
  • Calcium