From puffs to global Ca2+ signals: how molecular properties shape global signals.

in Chaos (2009), 19(3), 037111

The universality of Ca(2+) as second messenger in living cells is achieved by a rich spectrum of spatiotemporal cellular concentration dynamics. Ca(2+) release from internal storage compartments plays a ... [more ▼]

The universality of Ca(2+) as second messenger in living cells is achieved by a rich spectrum of spatiotemporal cellular concentration dynamics. Ca(2+) release from internal storage compartments plays a key role in shaping cytosolic Ca(2+) 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 Ca(2+) oscillations and its relevance for modeling Ca(2+) 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 Ca(2+) 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 Ca(2+) signaling. [less ▲]

Temperature and nitric oxide control spontaneous calcium transients in astrocytes.

in Cell calcium (2008), 43(3), 285-95

Transient spontaneous increases in the intracellular Ca2+ concentration have been frequently observed in astrocytes in cell culture and in acutely isolated slices from several brain regions. Recent in ... [more ▼]

Transient spontaneous increases in the intracellular Ca2+ concentration have been frequently observed in astrocytes in cell culture and in acutely isolated slices from several brain regions. Recent in vivo experiments, however, reported only a low frequency of spontaneous Ca2+ events in astrocytes. Since the ex vivo experiments were usually performed at temperatures lower than physiological body temperature, we addressed the question whether temperature could influence the spontaneous Ca2+ activity in astrocytes. Indeed, comparing the frequency and spike width of spontaneous Ca2+ transients in astrocytes at temperatures between 20 and 37 degrees C in culture as well as in acute cortical slices from mouse brain, revealed that spontaneous Ca2+ responses occurred frequently at low temperature and became less frequent at higher temperature. Moreover, the single Ca2+ events had a longer duration at low temperature. We found that nitric oxide (NO) mimicked the increase in spontaneous Ca2+ activity and that an NO-synthase inhibitor attenuated the effect of lowering the temperature. Thus, temperature and NO are major determinants of spontaneous astrocytic Ca2+ signalling. [less ▲]

Statistical properties and information content of calcium oscillations.

in Genome informatics. International Conference on Genome Informatics (2007), 18

Calcium is the most important second messenger in living cells serving as a critical link between a large variety of extracellular stimuli and the intracellular target. Often, the Ca(2+) signal is carried ... [more ▼]

Calcium is the most important second messenger in living cells serving as a critical link between a large variety of extracellular stimuli and the intracellular target. Often, the Ca(2+) signal is carried by [Ca(2+)] oscillations. Our recent studies have demonstrated that in contrast to traditional ideas Ca(2+) oscillations do not occur by simple synchronization of channel clusters opening and closing in an oscillatory fashion but originate from microscopic fluctuation caused by the stochastic binding of the ligands Ca(2+) and IP(3) to the receptor's binding sites. They are orchestrated spatially on the cell level by wave nucleation. In this paper we analyze the stochastic data and show how internal properties can be determined from global observations. Further, we analyze the information content of spontaneous and stimulated oscillations. [less ▲]