4.5 Article

CaV3.2 T-type channels mediate Ca2+ entry during oocyte maturation and following fertilization

Journal

JOURNAL OF CELL SCIENCE
Volume 128, Issue 23, Pages 4442-4452

Publisher

COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.180026

Keywords

Oocyte; Ca2+; T-type channel; Meiosis; Fertilization; Egg activation

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Funding

  1. Intramural Research Program of the National Institutes of Health, National Institutes of Environmental Health Sciences [1ZIAES102985]

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Initiation of mouse embryonic development depends upon a series of fertilization-induced rises in intracellular Ca2+. Complete egg activation requires influx of extracellular Ca2+; however, the channels that mediate this influx remain unknown. Here, we tested whether the alpha 1 subunit of the T-type channel Ca(V)3.2, encoded by Cacna1h, mediates Ca2+ entry into oocytes. We show that mouse eggs express a robust voltage-activated Ca2+ current that is completely absent in Cacna1h(-/-) eggs. Cacna1h(-/-) females have reduced litter sizes, and careful analysis of Ca2+ oscillation patterns in Cacna1h(-/-) eggs following in vitro fertilization (IVF) revealed reductions in first transient length and oscillation persistence. Total and endoplasmic reticulum (ER) Ca2+ stores were also reduced in Cacna1h(-/-) eggs. Pharmacological inhibition of Ca(V)3.2 in wild-type CF-1 strain eggs using mibefradil or pimozide reduced Ca2+ store accumulation during oocyte maturation and reduced Ca2+ oscillation persistence, frequency and number following IVF. Overall, these data show that Ca(V)3.2 T-type channels have prev8iously unrecognized roles in supporting the meiotic-maturation-associated increase in ER Ca2+ stores and mediating Ca2+ influx required for the activation of development.

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