期刊
JOURNAL OF CELL SCIENCE
卷 128, 期 23, 页码 4442-4452出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.180026
关键词
Oocyte; Ca2+; T-type channel; Meiosis; Fertilization; Egg activation
类别
资金
- Intramural Research Program of the National Institutes of Health, National Institutes of Environmental Health Sciences [1ZIAES102985]
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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