Simulations of the effects of inositol 1,4,5-trisphosphate 3-kinase and 5-phosphatase activities on Ca2+ oscillations

Cell Calcium. 1997 Nov;22(5):321-31. doi: 10.1016/s0143-4160(97)90017-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Calcium / metabolism*
  • Computer Simulation
  • Cricetinae
  • Inositol Polyphosphate 5-Phosphatases
  • Models, Biological
  • Phosphoric Monoester Hydrolases / metabolism*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*

Substances

  • Phosphotransferases (Alcohol Group Acceptor)
  • Inositol 1,4,5-trisphosphate 3-kinase
  • Phosphoric Monoester Hydrolases
  • Inositol Polyphosphate 5-Phosphatases
  • Calcium