Abstract
Astrocytes express a wide range of receptors for neurotransmitters and hormones that are coupled to increases in intracellular Ca2+ concentration, enabling them to detect activity in both neuronal and vascular networks. There is increasing evidence that astrocytes are able to discriminate between different Ca2+-linked stimuli, as the efficiency of some Ca2+ dependent processes – notably release of gliotransmitters – depends on the stimulus that initiates the Ca2+ signal. The spatiotemporal complexity of Ca2+ signals is substantial, and we here tested the hypothesis that variation in the kinetics of Ca2+ responses could offer a means of selectively engaging downstream targets, if agonists exhibited a “signature shape” in evoked Ca2+ response. To test this, astrocytes were exposed to three different receptor agonists (ATP, glutamate and histamine) and the resultant Ca2+ signals were analysed for systematic differences in kinetics that depended on the initiating stimulus. We found substantial heterogeneity between cells in the time course of Ca2+ responses, but the variation did not correlate with the type or concentration of the stimulus. Using a simple metric to quantify the extent of difference between populations, it was found that the variation between agonists was insufficient to allow signal discrimination. We conclude that the time course of global intracellular Ca2+ signals does not offer the cells a means for distinguishing between different neurotransmitters.
Highlights
Astrocytes are non-excitable cells of the central nervous system, which express a great many neurotransmitter and hormone receptors [1,2]
Primary cultures were prepared from cerebellum and cortex, and stained for the astrocyte marker glial fibrillary acidic protein (GFAP; Fig 1A,B)
Spatiotemporal complexity of Ca2+ responses. It is twenty seven years since neurotransmitter receptors were first described in astrocytes [14,15], and since that time, the number of Ca2+-linked receptors found to be expressed by the cells has expanded enormously
Summary
Astrocytes are non-excitable cells of the central nervous system, which express a great many neurotransmitter and hormone receptors [1,2]. Astrocytes are equipped to dynamically respond to signals in their microenvironment by changing cell morphology, gene expression profile, and releasing gliotransmitters to signal, in turn, to neurons, vascular cells and other glia These signalling pathways regulate the many roles of astrocytes in the brain – metabolic support of neurons, buffering of K+ concentration, reactive gliosis in response to injury and maintenance of the blood brain barrier [4,5,6,7] – but they raise the prospect that bidirectional communication between neurons and glia may play a computational role in the healthy brain [8,9]. The appropriate physiological response of a cell in situ to glutamate (a fast excitatory transmitter) may be expected to differ from its response to ATP (a diffusely acting inhibitory transmitter), or histamine (a neurotransmitter and inflammatory messenger) for example, and yet all of these agonists have been shown to trigger Ca2+ signals in glia [2]
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