Activation of mouse sperm T-type Ca2+ channels by adhesion to the egg zona pellucida.
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.
Arnoult
C
C
Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, MA 02111, USA.
Cardullo
R A
RA
Lemos
J R
JR
Florman
H M
HM
D000177:Acrosome / Q000187:drug effects / Q000502:physiology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D003272:Contraceptive Agents, Male; D004095:Dihydropyridines / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D010868:Pimozide / Q000494:pharmacology; D013084:Sperm-Ovum Interactions; D013094:Spermatozoa / Q000502:physiology*; D013737:Testis / Q000502:physiology; D015044:Zona Pellucida / Q000502:physiology*
D015220:Calcium Channels; D003272:Contraceptive Agents, Male; D004095:Dihydropyridines; D010868:Pimozide; D000584:Amiloride; D002118:Calcium