From puffs to global Ca2+ signals: How molecular properties shape global signals

The universality of Ca2+ as second messenger in living cells is achieved by a rich spectrum of spatiotemporal cellular concentration dynamics. Ca2+ release from internal storage compartments plays a key role in shaping cytosolic Ca2+ signals. Deciphering this signaling mechanism is essential for a deeper understanding of its physiological function and general concepts of cell signaling. Here, we review recent experimental findings demonstrating the stochasticity of Ca2+ oscillations and its relevance for modeling Ca2+ dynamics. The stochasticity arises by the hierarchical signal structure that carries molecular fluctuations of single channels onto the level of the cell leading to a stochastic medium as theoretically predicted. The result contradicts the current opinion of Ca2+ being a cellular oscillator. We demonstrate that cells use array enhanced coherence resonance to form rather regular spiking signals and that the oscillations carry information despite the involved stochasticity. The knowledge on the underlying mechanism also allows for determination of intrinsic properties from global observations. In the second part of the paper, we briefly survey different modeling approaches with regard to the experimental results. We focus on the dependence of the standard deviation on the mean period of the oscillations. It shows that limit cycle oscillations cannot describe the experimental data and that generic models have to include the spatial aspects of Ca2+ signaling.