A SINGLE-POOL INOSITOL 1,4,5-TRISPHOSPHATE-RECEPTOR-BASED MODEL FOR AGONIST-STIMULATED OSCILLATIONS IN CA2+ CONCENTRATION

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 Ca2+-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.