Fine tuning of cytosolic Ca2+ oscillations [version 1; referees: 3 approved]

Ca2+ oscillations, a widespread mode of cell signaling, were reported in non-excitable cells for the first time more than 25 years ago. Their fundamental mechanism, based on the periodic Ca2+ exchange between the endoplasmic reticulum and the cytoplasm, has been well characterized. However, how the kinetics of cytosolic Ca2+ changes are related to the extent of a physiological response remains poorly understood. Here, we review data suggesting that the downstream targets of Ca2+ are controlled not only by the frequency of Ca2+ oscillations but also by the detailed characteristics of the oscillations, such as their duration, shape, or baseline level. Involvement of non-endoplasmic reticulum Ca2+ stores, mainly mitochondria and the extracellular medium, participates in this fine tuning of Ca2+ oscillations. The main characteristics of the Ca2+ exchange fluxes with these compartments are also reviewed