Figure 4. A. IP₃ receptors lateral mobility in ER patches and reticular ER.

Fluorescence recovery after photobleaching (FRAP) in oocytes and eggs expressing GFP-IP₃ receptor (n = 7–8; mean±SE). The bleaching ROIs in eggs were positioned over ER patches or reticular ER. Recovery kinetics were fitted with a monoexponential decay function. Recovery kinetics show that the lateral mobility of IP₃ receptors is comparable within ER patches and the reticular ER. B–D. Mathematical modeling. Modeling the time delay in Ca²⁺ release as a function of IP₃ receptor cluster size. As IP₃ receptor cluster size increases the delay in response to an IP₃ pulse decreases. C. Modeling Ca²⁺ release spatial and amplitude distribution from two IP₃ receptor clusters of varying size (20 and 1000) in response to a sub-threshold IP₃ pulse. D. Simulation of the dependence of Ca²⁺ release within an IP₃ receptor cluster as a function of IP₃ concentration for varying Ca²⁺ diffusion coefficients. Lowering the Ca²⁺ diffusion coefficient results in less Ca²⁺-dependent cooperativity between neighboring receptors. Decreasing Ca²⁺ diffusion coefficient leads to decreased sensitivity of IP₃ receptors as illustrated by the threshold IP₃ concentration required to initiate Ca²⁺ release.