Abstract
Mean field models are often useful approximations to biological systems, but sometimes, they can yield misleading results. In this work, we compare mean field approaches with stochastic models of intracellular calcium release. In particular, we concentrate on calcium signals generated by the concerted opening of several clustered channels (calcium puffs). To this end we simulate calcium puffs numerically and then try to reproduce features of the resulting calcium distribution using mean field models were all the channels open and close simultaneously. We show that an unrealistic non-linear relationship between the current and the number of open channels is needed to reproduce the simulated puffs. Furthermore, a single channel current which is five times smaller than the one of the stochastic simulations is also needed. Our study sheds light on the importance of the stochastic kinetics of the calcium release channel activity to estimate the release fluxes.
Highlights
An important problem in different areas of science is to relate phenomena that occur at different scales
The results we presented in Bruno et al (2010) and those of Rose et al (2006) could be explained by a model in which the total calcium current released through a cluster of IP3Rs during a puff is a non-linear function of the number of open channels: linear when the number is small and proportional to the square root of the number of channels for larger puffs
The present study shows the limitations of mean field models and the importance of including a detailed description of the intra-cluster dynamics in order to infer realistic single channel properties from collective signals such as puffs
Summary
An important problem in different areas of science is to relate phenomena that occur at different scales. As a result of the spatial organization of channels and the process of Ca2+-induced Ca2+-release (CICR), cytosolic Ca2+ signals display a hierarchical spatiotemporal organization which in some cells (e.g., oocytes) have length scales that span over six orders of magnitude (Callamaras and Parker, 1994; Mak and Foskett, 1997; Shuai and Jung, 2003a). The spatial resolution of conventional light microscopy is limited by diffraction This determines that features below the 250-nm length scales are unobservable in typical confocal images. The need of using TIRF to guarantee a good axial resolution restricts the application of this approach to cells, as those of the human neuroblastoma SH-SY5Y cell line, where IP3Rs are close enough to the plasma membrane
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