Role of Ca²⁺ oscillations at fertilization in mammals: In all mammalian species, sperm-egg fusion leads to repetitive increases in the level of cytosolic Ca²⁺. These oscillations play an important role in the relief of the egg from its arrested state. To undestand the mechanism by wich egg development could be optimized by an appropriate pattern of Ca²⁺ oscillations, the interactions between the cell cycle and the intracellular Ca²⁺ dynamics have to be investigated. On the basis of the available experimental datas, a model involving the well-known activation of calmodulin-dependent kinase II by Ca²⁺ has been developed. To account for experimental observations, it has to be assumed that CaMKII interferes with the cell cycle oscillator at two distinct levels, the 2 pathways being characterized by different kinetics. The model thus accounts for the observed dependence of the time of entry in interphase on the frequency of the Ca²⁺ spikes, as well as for the possible entry in metaphase III, a pathological state of the egg which results from an insufficient activation by Ca²⁺. Possible mechanism for bursting-type complex Ca²⁺ oscillations: In most cases, Ca²⁺ oscillations appear as periodic increases of the level of cytosolic Ca²⁺ from the basal level up to a high concentration of the order of 1 µM. In response to specific agonists, some cells as hepatocytes display oscillations of the bursting type, i.e. a large-amplitude Ca²⁺ spike followed by small-amplitude variations around a plateau-level. The possible mechanisms of such complex oscillations have been investigated. Amoung various possibilities, a model based on the interplay between Ca²⁺-induced Ca²⁺ release and the Ca²⁺-activated metabolism of InsP3 by 3-kinase displays interesting properties. In particular, it can explain the experimental observation that Ca²⁺ oscillations are very little affected by the overexpression of InsP3 3-kinase, one of the two enzymes responsible for InsP3 degradation.

Back to Workshop Schedule