Contribution of calcium fluxes to astrocyte spontaneous calcium oscillations in deterministic and stochastic models

摘要

Highlights•Proposed novel biophysical model for spontaneous Ca2+oscillation in astrocytes.•Investigated the stochastic effect w.r.t voltage gated Ca2+channel noise and IP3R binding dynamic.•Explained why seemingly conflicting flux contribution conclusions are obtained in experiments.AbstractSpontaneous Ca2+oscillation is a special kind of astrocyte signal that is crucial in several brain functions. However, the underlying mechanism of its initiation is still unclear. Experimental investigations reveal quite different results of the contribution of Ca2+influxes from the extracellular space. We developed a new biophysical model, which includes two kinds of extracellular Ca2+influx: through voltage gated Ca2+channels and through capacitative Ca2+entry. Besides, two stochastic models are constructed to discuss the influence of channel noise in voltage gated influx and stochastic IP3receptor dynamics on the contribution of Ca2+fluxes. Simulation results reveal that the contribution of a given flux can be considerably strengthened or weakened by special cellular states, such as the change of membrane potential, inter-flux feedback; the special cellular condition (e.g. endoplasmic reticulum depletion, other flux inhibition). In stochastic environment, the contribution of fluxes may be strongly altered and the respond of different fluxes varies qualitatively. Our results may help to understand the different results obtained in experiments.