A dynamic model of the type-2 inositol trisphosphate receptor

The dynamic properties of the inositol (1,4,5)-trisphosphate (I[P.sub.3]) receptor are crucial for the control of intracellular [Ca.sup.2+], including the generation of [Ca.sup.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 I[P.sub.3] receptor and fit the model to dynamic and steady-state experimental data from type-2 I[P.sub.3] receptors. Our results indicate that, (i) [Ca.sup.2+] binds to the receptor using saturating, not mass-action, kinetics; (i) [Ca.sup.2+] decreases the rate of I[P.sub.3] binding while simultaneously increasing the steady-state sensitivity of the receptor to I[P.sub.3]; (iii) the rate of [Ca.sup.2+]-induced receptor activation increases with [Ca.sup.2+] and is faster than [Ca.sup.2+]-induced receptor inactivation; and (iv) I[P.sub.3] receptors are sequentially activated and inactivated by [Ca.sup.2+] even when I[P.sub.3] is bound. Our results emphasize that measurement of steady-state properties alone is insufficient to characterize the functional properties of the receptor.