| First Author | Bernhardt ML | Year | 2015 |
| Journal | J Cell Sci | Volume | 128 |
| Issue | 23 | Pages | 4442-52 |
| PubMed ID | 26483387 | Mgi Jnum | J:233913 |
| Mgi Id | MGI:5788370 | Doi | 10.1242/jcs.180026 |
| Citation | Bernhardt ML, et al. (2015) CaV3.2 T-type channels mediate Ca(2)(+) entry during oocyte maturation and following fertilization. J Cell Sci 128(23):4442-52 |
| abstractText | Initiation of mouse embryonic development depends upon a series of fertilization-induced rises in intracellular Ca(2+). Complete egg activation requires influx of extracellular Ca(2+); however, the channels that mediate this influx remain unknown. Here, we tested whether the alpha1 subunit of the T-type channel CaV3.2, encoded by Cacna1h, mediates Ca(2+) entry into oocytes. We show that mouse eggs express a robust voltage-activated Ca(2+) current that is completely absent in Cacna1h(-/-) eggs. Cacna1h(-/-) females have reduced litter sizes, and careful analysis of Ca(2+) oscillation patterns in Cacna1h(-/-) eggs following in vitro fertilization (IVF) revealed reductions in first transient length and oscillation persistence. Total and endoplasmic reticulum (ER) Ca(2+) stores were also reduced in Cacna1h(-/-) eggs. Pharmacological inhibition of CaV3.2 in wild-type CF-1 strain eggs using mibefradil or pimozide reduced Ca(2+) store accumulation during oocyte maturation and reduced Ca(2+) 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 Ca(2+) stores and mediating Ca(2+) influx required for the activation of development. |
