A single-pool inositol 1,4,5-trisphosphate-receptor-based model for agonist-stimulated oscillations in Ca2+ concentration

Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9895-9. doi: 10.1073/pnas.89.20.9895.

Abstract

Relying on quantitative measurements of Ca2+ activation and inhibition of the inositol 1,4,5-trisphosphate (IP3) receptor in the endoplasmic reticulum, we construct a simplified kinetic model to describe the properties of this channel. Selecting rate constants to fit key kinetic and equilibrium data, we find that the model reproduces a variety of in vivo and in vitro experiments. In combination with Ca(2+)-ATPase activity for Ca2+ uptake into the endoplasmic reticulum, the model leads to cytoplasmic oscillations in Ca2+ concentration at fixed IP3 concentration and only a single pool of releasable Ca2+, the endoplasmic reticulum. Incorporation of a positive-feedback mechanism of Ca2+ on IP3 production by phospholipase C enriches the properties of the oscillations and leads to oscillations in Ca2+ concentration accompanied by oscillations in IP3 concentration. We discuss the possible significance of these results for the interpretation of experiments.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Calcium / metabolism*
  • Calcium Channels / physiology*
  • Feedback
  • Inositol 1,4,5-Trisphosphate / metabolism*
  • Inositol 1,4,5-Trisphosphate Receptors
  • Ion Channel Gating
  • Kinetics
  • Models, Theoretical
  • Periodicity
  • Receptors, Cell Surface / physiology*
  • Receptors, Cytoplasmic and Nuclear*
  • Second Messenger Systems
  • Signal Transduction

Substances

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