Inositol 1,4,5-Trisphosphate Receptor 1 Degradation in Mouse Eggs and Impact on [Ca2+](i) Oscillations

The initiation of normal embryo development depends on the completion of all events of egg activation. In all species to date, egg activation requires an increase(s) in the intracellular concentration of calcium ([Ca2+](i)), which is almost entirely mediated by inositol 1,4,5-trisphosphate receptor I (IP3RI). In mammalian eggs, fertilization-induced [Ca2+](i) responses exhibit a periodic pattern that are called [Ca2+](i) oscillations. These [Ca2+](i) oscillations are robust at the beginning of fertilization, which occurs at the second metaphase of meiosis, but wane as zygotes approach the pronuclear stage, time after which in the mouse oscillations cease altogether. Underlying this change in frequency are cellular and biochemical changes associated with egg activation, including degradation of IP3RI, progression through the cell cycle, and reorganization of intracellular organelles. In this study, we investigated the system requirements for IP3RI degradation and examined the impact of the IP3RI levels on the pattern of [Ca2+](i) oscillations. Using microinjection of IP3 and of its analogs and conditions that prevent the development of [Ca2+](i) oscillations, we show that IP3RI degradation requires uniform and persistently elevated levels of IP3. We also established that progressive degradation of the IP3RI results in [Ca2+](i) oscillations with diminished periodicity while a near complete depletion of IP(3)RIs precludes the initiation of [Ca2+](i) oscillations. These results provide insights into the mechanism involved in the generation of [Ca2+](i) oscillations in mouse eggs. J. Cell. Physiol. 222: 238-247, 2010. (C) 2009 Wiley-Liss, Inc.