Hierarchic Stochastic Modelling Applied to Intracellular Ca(2+) Signals

Important biological processes like cell signalling and gene expression have noisy components and are very complex at the same time. Mathematical analysis of such systems has often been limited to the study of isolated subsystems, or approximations are used that are difficult to justify. Here we extend a recently published method (Thurley and Falcke, PNAS 2011) which is formulated in observable system configurations instead of molecular transitions. This reduces the number of system states by several orders of magnitude and avoids fitting of kinetic parameters. The method is applied to [Image: see text] signalling. [Image: see text] is a ubiquitous second messenger transmitting information by stochastic sequences of concentration spikes, which arise by coupling of subcellular [Image: see text] release events (puffs). We derive analytical expressions for a mechanistic [Image: see text] model, based on recent data from live cell imaging, and calculate [Image: see text] spike statistics in dependence on cellular parameters like stimulus strength or number of [Image: see text] channels. The new approach substantiates a generic [Image: see text] model, which is a very convenient way to simulate [Image: see text] spike sequences with correct spiking statistics.