title: High-throughput analysis of calcium signalling kinetics in astrocytes stimulated with different neurotransmitters.
abstract: Astrocytes express a wide range of receptors for neurotransmitters and hormones that are coupled to increases in intracellular Ca(2+) concentration, enabling them to detect activity in both neuronal and vascular networks. There is increasing evidence that astrocytes are able to discriminate between different Ca(2+)-linked stimuli, as the efficiency of some Ca(2+) dependent processes--notably release of gliotransmitters--depends on the stimulus that initiates the Ca(2+) signal. The spatiotemporal complexity of Ca(2+) signals is substantial, and we here tested the hypothesis that variation in the kinetics of Ca(2+) responses could offer a means of selectively engaging downstream targets, if agonists exhibited a "signature shape" in evoked Ca(2+) response. To test this, astrocytes were exposed to three different receptor agonists (ATP, glutamate and histamine) and the resultant Ca(2+) 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 Ca(2+) 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 Ca(2+) signals does not offer the cells a means for distinguishing between different neurotransmitters.
authors: Laboratory of Molecular Signalling, The Babraham Institute, Babraham, Cambridge, United Kingdom.
authors: Laura R
authors: LR
authors: James
authors: Simon
authors: S
authors: Andrews
authors: Simon
authors: S
authors: Walker
authors: Paula R S
authors: PR
authors: de Sousa
authors: Aaron
authors: A
authors: Ray
authors: Noah A
authors: NA
authors: Russell
authors: Tomas C
authors: TC
authors: Bellamy
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D001253:Astrocytes / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D018698:Glutamic Acid / Q000494:pharmacology; D057166:High-Throughput Screening Assays / Q000379:methods*; D006632:Histamine / Q000494:pharmacology; D007700:Kinetics; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D017981:Receptors, Neurotransmitter / Q000819:agonists*
chemical_list: D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter; D018698:Glutamic Acid; D006632:Histamine; D000255:Adenosine Triphosphate