Simulations of the effects of inositol 1,4,5-trisphosphate 3-kinase and 5-phosphatase activities on Ca2+ oscillations.
Inositol 1,4,5-trisphosphate (Ins-1,4,5-P3) 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-1,4,5-P3 metabolizing enzymes (Ins-1,4,5-P3 3-kinase and 5-phosphatase) on the temporal pattern of Ca2+ oscillations has been investigated. On the basis of the well-documented Ins-1,4,5-P3 3-kinase stimulation by the Ca2+/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-P3 and, thereby, the occurrence and frequency of Ca2+ 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 Ca2+ 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-1,4,5-P3 3-kinase activities.
Dupont
G
G
Unité de Chronobiologie Théorique, Faculté des Sciences, Université Libre de Bruxelles, Belgium. gdupont@ulb.ac.be
Erneux
C
C
D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D003198:Computer Simulation; D006224:Cricetinae; D000072181:Inositol Polyphosphate 5-Phosphatases; D008954:Models, Biological; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*
D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; D002118:Calcium