Figure 7.

Control of Ca²⁺ spikes by IP₃ production in pancreatic acinar cells. Increases in [IP₃]_i can trigger spread of Ca²⁺ spikes (Ca²⁺ waves) by sequential activation of IP₃ receptors, if there is a spatial gradient of IP₃ sensitivity across the cell and if the rate of IP₃ production is slower than that of the CICR-mediated Ca²⁺ spikes. For simplicity, if we assume that the CICR mechanism occurred instantaneously, the distribution of [Ca²⁺]_i is expressed as a function of the IP₃ sensitivity at a specific place, K _IP3(x), and of [IP₃]_i at a specific time, [IP₃]_i (t). [Ca²⁺]_i is determined by a balance between CICR-amplified Ca²⁺ release and Ca²⁺ removal mechanisms. When [IP₃]_i is small, local Ca²⁺ spikes result; when [IP₃]_i is large, Ca²⁺ spikes spread further, and generate global Ca²⁺ spikes in a dose-dependent manner. More rapid increases in [IP₃]_i result in a faster spread of Ca²⁺ spikes. Thus, kinetics of IP₃ production play a key role in the amplitude, extent, and time course of Ca²⁺ spikes. The same mechanism is operative in the generation of Ca²⁺ spikes in those cells with heterogenous IP₃ receptors, even though there is no spatial gradient in IP₃ receptors.