Essential role of the inositol 1,4,5-trisphosphate receptor/Ca2+ release channel in Ca2+ waves and Ca2+ oscillations at fertilization of mammalian eggs

Abstract

At fertilization mammalian eggs exhibit repetitive rises in the cytoplasmic Ca2+ concentration (Ca2+ oscillations), associated with propagating Ca2+ waves in the initial responses. The Ca2+ oscillation causes cortical granule exocytosis and resumption of second meiosis and affects later embryonic development. Recent studies using a function-blocking monoclonal antibody to the inositol 1,4,5-trisphosphate (InsP3) receptor/Ca2+ release channel demonstrated direct evidence that InsP3-induced Ca2+ release (IICR) from intracellular stores operates at fertilization of the hamster egg and that IICR is essential in the initiation, propagation, and oscillation of the sperm-induced Ca2+ rises. Ca(2+)-induced Ca2+ release (CICR) has also been suggested, but a sensitizing action of Ca2+ on the InsP3 receptor, i.e., Ca(2+)-sensitized IICR, can serve as a regenerative process of Ca2+ release and could be the basis for Ca2+ waves and Ca2+ oscillations. It is now apparent that signal transduction at fertilization is dependent on sperm-stimulated activation of phospholipase C which causes hydrolysis of phosphatidylinositol bisphosphate and production of InsP3, leading to IICR. On the other hand, Ca2+ signaling at fertilization of the sea urchin egg may also involve ryanodine receptor-mediated CICR.