PT  - JOURNAL ARTICLE
AU  - Bernhardt, Miranda L.
AU  - Zhang, Yingpei
AU  - Erxleben, Christian F.
AU  - Padilla-Banks, Elizabeth
AU  - McDonough, Caitlin E.
AU  - Miao, Yi-Liang
AU  - Armstrong, David L.
AU  - Williams, Carmen J.
TI  - Ca<sub>V</sub>3.2 T-type channels mediate Ca<sup>2+</sup> entry during oocyte maturation and following fertilization
AID  - 10.1242/jcs.180026
DP  - 2015 Dec 01
TA  - Journal of Cell Science
PG  - 4442--4452
VI  - 128
IP  - 23
4099  - http://jcs.biologists.org/content/128/23/4442.short
4100  - http://jcs.biologists.org/content/128/23/4442.full
SO  - J. Cell Sci.2015 Dec 01; 128
AB  - 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 α1 subunit of the T-type channel CaV3.2, 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 CaV3.2 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 CaV3.2 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.