Ca²⁺ release from intracellular stores via the inositol 1,4,5-trisphosphate receptor (IP₃R) regulates a vast array of important cell functions including smooth muscle contraction, secretion, immunity, fertilization and synaptic plasticity. The versatility of Ca²⁺ signals is thought to be based on the complexity of signals that can be coded by the release of Ca²⁺ from the intracellular stores, i.e. Ca²⁺ release may be localised and transient (Ca²⁺ puffs), may propagate regeneratively across a cell (Ca²⁺ waves) and may be repeated periodically (Ca²⁺ oscillations). These Ca²⁺ signals convey distinct information depending on their spatiotemporal patterns. The dynamic changes in the intracellular Ca²⁺ concentration ([Ca²⁺]_i) are thought to require the presence of certain forms of feedback mechanism during Ca²⁺ mobilisation. Interestingly, IP₃R activities are sensitive to [Ca²⁺]_i at submicromolar to micromolar concentrations in a biphasic manner. Therefore, it is possible that the Ca²⁺-mediated feedback regulation of Ca²⁺ release contributes to the generation of spatiotemporal dynamics of Ca²⁺ signals. We identified the Ca²⁺ sensor region of the IP₃R, and the substitution of glutamate at position 2100 of type 1 IP₃R by aspartate resulted in a 10-fold decrease in Ca²⁺ sensitivity (Miyakawa, 2001). In agonist-stimulated cells expressing the low-Ca²⁺ sensitivity mutant IP₃R, the rates of increase in [Ca²⁺]_i were markedly reduced and Ca²⁺ oscillations were abolished. These results indicate that the Ca²⁺-mediated feedback regulation of IP₃R is important for the generation of spatiotemporal patterns of Ca²⁺ signals. Another candidate molecule that may be under a Ca²⁺-mediated feedback regulation is IP₃. We succeeded in generating an IP₃ indicator based on the pleckstrin homology domain of phospholipase C-δ1 (Hirose et al. 1999). Using this new method, we showed that the IP₃ production is also dependent on [Ca²⁺]_i, and indeed we found IP₃ oscillations that were synchronizing with Ca²⁺ oscillations. Furthermore, we showed that the depolarisation-mediated influx of Ca²⁺ induces IP₃ production in cerebellar Purkinje cells (Okubo et al. 2001). These results demonstrate that both IP₃ production and Ca²⁺ release are under the feedback control of [Ca²⁺]_i, which is an important molecular basis of the complex spatiotemporal patterns of Ca²⁺ signals.