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