FIG. 1.

Schematic of the behaviors of inositol trisphosphate receptor (InsP₃R) channels in the presence of increasing concentrations of InsP₃. InsP₃Rs are shown arranged in clusters that form discrete release sites within the continuous endoplasmic reticulum. A: at low [InsP₃] during weak agonist stimulation, few receptors (in green) bind InsP₃. Others (in yellow) are not InsP₃ liganded and therefore not activated. Consequently, highly localized small Ca²⁺ signals (“blips”) are generated by Ca²⁺ released through a single or few InsP₃R channels raising cytoplasmic Ca²⁺ concentration (shown in red). B: at higher levels of [InsP₃], coordinated openings of several channels (InsP₃ liganded) within a cluster is triggered by Ca²⁺ release from one channel acting as an activating ligand to stimulate gating of nearby channels through a process of Ca²⁺-induced Ca²⁺ release (CICR). C: even higher [InsP₃] evokes global propagating Ca²⁺ signals (waves). Ca²⁺ released at one cluster can trigger Ca²⁺ release at adjacent clusters by CICR, leading to the generation of Ca²⁺ waves that propagate by successive cycles of Ca²⁺ release, diffusion, and CICR. [Figure kindly supplied by I. Parker and N. Callamaras. Adapted from Parker et al. (358).]