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PMID: 10359785 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Control of the low voltage-activated calcium channel of mouse sperm by egg ZP3 and by membrane hyperpolarization during capacitation.

Arnoult C, Kazam IG, Visconti PE, Kopf GS, Villaz M, Florman HM

Abstract

Sperm adhesion to egg zonae pellucidae initiates sperm acrosome reactions, an exocytotic event that is an early step during fertilization. Previously, it was suggested that zona pellucida-evoked Ca2+ entry into sperm through low voltage-activated Ca2+ channels is an essential step in acrosome reactions, based on the inhibitory effects of Ca2+ channel antagonists. However, analysis of this channel is limited by the inability to apply electrophysiological methods directly to sperm. In this report, optical methods of determining membrane potential and internal Ca2+ levels were used to demonstrate that (i) contact with zonae pellucidae activates a transient Ca2+ response in sperm that has a time course and antagonist sensitivity anticipated of low voltage-activated Ca2+ channels; (ii) these channels are unavailable for opening in uncapacitated sperm because of voltage-dependent, steady state inactivation; (iii) membrane hyperpolarization during sperm capacitation is sufficient to recruit channels into a closed state, from which they are available for opening during fertilization; and (iv) channel conductance state may be a factor in determines the efficacy with which channel antagonists inhibit fertilization. This study provides evidence for the activation of sperm Ca2+ channels during gamete adhesion and offers a mechanism that may account for aspects of the regulation of sperm fertility during capacitation through the control of channel availability. Finally, these results suggest that channel conductance state may be a central feature in the design of channel antagonists that inhibit sperm function.

MeSH Terms
Animals Calcium Channels/physiology Egg Proteins/analysis,pharmacology Female Ion Channel Gating/drug effects Male Membrane Glycoproteins/analysis,pharmacology,physiology Membrane Potentials/drug effects Mice Receptors, Cell Surface Sperm Capacitation/physiology Sperm-Ovum Interactions/physiology Spermatozoa/physiology Zona Pellucida Zona Pellucida Glycoproteins
Chemicals
Calcium Channels Egg Proteins Membrane Glycoproteins Receptors, Cell Surface Zona Pellucida Glycoproteins Zp3 protein, mouse
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Arnoult C
Centre d'Etudes de Grenoble, Departement de Biologie Moleculaire et Structurale, 38054 Grenoble, France.
Kazam I G
Visconti P E
Kopf G S
Villaz M
Florman H M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1999-06-08
Pages
6757-62
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC21988
Subset
IM
Grants
NICHD NIH HHS · P01 HD006274 · United States
NICHD NIH HHS · HD06274 · United States
NICHD NIH HHS · HD32177 · United States
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