A dynamic model of the type-2 inositol trisphosphate receptor

Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2398-403. doi: 10.1073/pnas.032281999. Epub 2002 Feb 12.


The dynamic properties of the inositol (1,4,5)-trisphosphate (IP(3)) receptor are crucial for the control of intracellular Ca(2+), including the generation of Ca(2+) oscillations and waves. However, many models of this receptor do not agree with recent experimental data on the dynamic responses of the receptor. We construct a model of the IP(3) receptor and fit the model to dynamic and steady-state experimental data from type-2 IP(3) receptors. Our results indicate that, (i) Ca(2+) binds to the receptor using saturating, not mass-action, kinetics; (ii) Ca(2+) decreases the rate of IP(3) binding while simultaneously increasing the steady-state sensitivity of the receptor to IP(3); (iii) the rate of Ca(2+)-induced receptor activation increases with Ca(2+) and is faster than Ca(2+)-induced receptor inactivation; and (iv) IP(3) receptors are sequentially activated and inactivated by Ca(2+) even when IP(3) is bound. Our results emphasize that measurement of steady-state properties alone is insufficient to characterize the functional properties of the receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Calcium / metabolism
  • Calcium / pharmacology
  • Calcium Channels / chemistry*
  • Calcium Channels / metabolism*
  • Dose-Response Relationship, Drug
  • Inositol 1,4,5-Trisphosphate Receptors
  • Kinetics
  • Models, Chemical
  • Oscillometry
  • Protein Binding
  • Receptors, Cytoplasmic and Nuclear / chemistry*
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Time Factors
  • Xenopus


  • Calcium Channels
  • Inositol 1,4,5-Trisphosphate Receptors
  • Receptors, Cytoplasmic and Nuclear
  • Calcium