Simulations of the effects of inositol 1,4,5=trisphosphate 3-kinase and S-phosphatase activities on Ca+ oscillations

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Summary lnositol 1,4,5-trisphosphate (Ins-l ,4,5-P,) is responsible for Ca2+ mobilization in response to external stimulation in many cell types. The latter phenomenon often occurs as repetitive Ca2+ spikes. In this study, the effect of the two Ins-l ,4,5-P, metabolizing enzymes (Ins-l ,4,5-P, 3-kinase and 5-phosphatase) on the temporal pattern of Ca*+ oscillations has been investigated. On the basis of the well-documented Ins-1,4,5-P, 3-kinase stimulation by the Ca*+/calmodulin complex and of the experimentally-determined kinetic characteristics of these enzymes, we predict that 5-phosphatase primarily controls the levels of Ins-1,4,5-P,and, thereby, the occurrence and frequency of Ca*+ oscillations. Consequently, the model reproduces the experimental observation performed in Chinese hamster ovary cells that 5-phosphatase overexpression has a much more pronounced effect on the pattern of Ca*+ oscillations than 3- kinase overexpression. We also investigated, in more detail, under which conditions a similar effect could be observed in other cell types expressing various Ins-l ,4,5-P, 3-kinase activities. 
Hanne Nielsen <>
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