Abstract
BackgroundAstrocytes were conceived for decades only as supporting cells of the brain. However, the observation of Ca2+ waves in astrocyte synctitia, their neurotransmitter receptor expression and gliotransmitter secretion suggested a role in information handling, conception that has some controversies. Synaptic Neuron-Astrocyte metabotropic communication mediated by Inositol tris-phosphate (SN-AmcIP3) is supported by different reports. However, some models contradict this idea and Ca2+ stores are 1000 ± 325 nm apart from the Postsynaptic Density in the Perisynaptic Astrocyte Projections (PAP’s), suggesting that SN-AmcIP3 is extrasynaptic. However, this assumption does not consider IP3 Diffusion Coefficient (Dab), that activates IP3 Receptor (IP3R) releasing Ca2+ from intracellular stores.ResultsIn this work we idealized a model of a PAP (PAPm) to perform an order of magnitude analysis of IP3 diffusion using a transient mass diffusion model. This model shows that IP3 forms a concentration gradient along the PAPm that reaches the steady state in milliseconds, three orders of magnitude before IP3 degradation. The model predicts that IP3 concentration near the Ca2+ stores may activate IP3R, depending upon Phospholipase C (PLC) number and activity. Moreover, the PAPm supports that IP3 and extracellular Ca2+ entry synergize to promote global Ca2+ transients.ConclusionThe model presented here indicates that Ca2+ stores position in PAP’s does not limit SN-AmcIP3.
Highlights
Astrocytes were conceived for decades only as supporting cells of the brain
T 1⁄4 tL^2=Diffusion Coefficient (Dab): the same profiles of concentration gradients are potentially reached by different solutes for the same Perisynaptic astrocyte projection model (PAPm) in times dependent upon their Dab
Number of Inositol tris-phosphate (IP3) molecules in the vicinity of PAPm Ca2+ stores In the framework of neurobiology, the numerical solution given above for Eq 2 is interesting when it is interpreted in actual IP3 numbers within the PAPm and time values, since it offers an insight into what may happen with Phospholipase C (PLC) metabotropic signalling in an actual Perisynaptic Astrocyte Projection (PAP)
Summary
Astrocytes were conceived for decades only as supporting cells of the brain. the observation of Ca2+ waves in astrocyte synctitia, their neurotransmitter receptor expression and gliotransmitter secretion suggested a role in information handling, conception that has some controversies. The neurocentric theory denied for decades the role of neuroglia on information handling within the Central Nervous System (CNS), believing that neurons were the only type of cell involved in such function [1]. In this scheme, astrocytes were considered supporting cells for neuronal metabolism, survival and function. Astrocytes were considered supporting cells for neuronal metabolism, survival and function This conception started to change 25 years ago, when it was reported that astrocytes communicate through Ca2+ waves that travel through their sinctitia [2].
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