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Spatiotemporal dynamics of Ca2+ signaling and its physiological roles.

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Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.


Changes in the intracellular Ca(2+) concentration regulate numerous cell functions and display diverse spatiotemporal dynamics, which underlie the versatility of Ca(2+) in cell signaling. In many cell types, an increase in the intracellular Ca(2+) concentration starts locally, propagates within the cell (Ca(2+) wave) and makes oscillatory changes (Ca(2+) oscillation). Studies of the intracellular Ca(2+) release mechanism from the endoplasmic reticulum (ER) showed that the Ca(2+) release mechanism has inherent regenerative properties, which is essential for the generation of Ca(2+) waves and oscillations. Ca(2+) may shuttle between the ER and mitochondria, and this appears to be important for pacemaking of Ca(2+) oscillations. Importantly, Ca(2+) oscillations are an efficient mechanism in regulating cell functions, having effects supra-proportional to the sum of duration of Ca(2+) increase. Furthermore, Ca(2+) signaling mechanism studies have led to the development of a method for specific inhibition of Ca(2+) signaling, which has been used to identify hitherto unrecognized functions of Ca(2+) signals.

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