Divalent cation influx and calcium homeostasis in germinal vesicle mouse oocytes. (May 2020)

• Record Type: Journal Article
• Authors: Ardestani, Goli; Mehregan, Aujan; Fleig, Andrea; Horgen, F. David; Carvacho, Ingrid; Fissore, Rafael A.
• Is Part Of: Cell calcium. Volume 87(2020)
• Publication Date: 2020-05
• Subjects: Calcium -- Influx -- Signaling -- TRPV3 -- TRPM7 -- Cav3.2 -- Meiosis; Calcium -- Metabolism -- Periodicals; Vertebrates -- Physiology -- Periodicals; Calcium -- Physiological effect -- Periodicals; Cell physiology -- Periodicals; Calcium in the body -- Periodicals; 572.516
• DOI: 10.1016/j.ceca.2020.102181
• Languages: English
• ISSNs: 0143-4160

Abstract

Graphical abstract: Highlights: CaV 3.2, TRPM7 and TRPV3 channels differentially mediate the influx of Ca 2+ and other divalent cations in GV oocytes. CaV 3.2 and TRPM7 are responsible for most of the steady-state and acute Ca 2+ influx, respectively. CaV 3.2 supports the majority of Sr 2+ influx, TRPM7 the majority of Ni 2+ influx, and both channels mediate Mn 2+ influx. CaV 3.2 maintains Ca 2+ levels in the TG-sensitive ER stores, but CaV 3.2 and TRPV3 sustain the total internal Ca 2+ stores, which are emptied by IO. 2-APB and Ni 2+ act as both agonists and antagonists of divalent cation influx in GV oocytes. Abstract: Prior to maturation, mouse oocytes are arrested at the germinal vesicle (GV) stage during which they experience constitutive calcium (Ca 2+ ) influx and spontaneous Ca 2+ oscillations. The oscillations cease during maturation but Ca 2+ influx continues, as the oocytes' internal stores attain maximal content at the culmination of maturation, the metaphase II stage. The identity of the channel(s) that underlie this Ca 2+ influx has not been completely determined. GV and matured oocytes are known to express three Ca 2+ channels, CaV 3.2, TRPV3 and TRPM7, but females null for each of these channels are fertile and their oocytes display minor modifications in Ca 2+ homeostasis, suggesting a complex regulation of Ca 2+ influx. To define the contribution of these channels at the GV stage, we used different divalent cations, pharmacological inhibitors and genetic models. We found that the three channels are active at this stage. CaV 3.2 and TRPM7 channels contributed the majority of Ca 2+ influx, as inhibitors and oocytes from homologous knockout (KO) lines showed severely reduced Ca 2+ entry. Sr 2+ influx was promoted by CaV 3.2 channels, as Sr 2+ oscillations were negligible in CaV 3.2 -KO oocytes but robust in control and Trpv3 -KO GV oocytes. Mn 2+ entry relied on expression of CaV 3.2 and TRPM7 channels, but Ni 2+ entry depended on the latter. CaV 3.2 and TRPV3 channels combined to fill the Ca 2+ stores, although CaV 3.2 was the most impactful. Studies with pharmacological inhibitors effectively blocked the influx of divalent cations, but displayed off-target effects, and occasionally agonist-like properties. In conclusion, GV oocytes express channels mediating Ca 2+ and other divalent cation influx that are pivotal for fertilization and early development. These channels may serve as targets for intervention to improve the success of assisted reproductive technologies.