high-throughput analysis of calcium signalling kinetics in astrocytes stimulated with different neurotransmitters钙信号的高通量分析动力学在星形胶质细胞刺激不同的神经递质.pdfVIP

High-Throughput Analysis of Calcium Signalling Kinetics in Astrocytes Stimulated with Different Neurotransmitters 1 2 1 3 3 4 Laura R. James , Simon Andrews , Simon Walker , Paula R. S. de Sousa , Aaron Ray , Noah A. Russell , Tomas C. Bellamy1,3* 1 Laboratory of Molecular Signalling, The Babraham Institute, Babraham, Cambridge, United Kingdom, 2 Bioinformatics Group, The Babraham Institute, Babraham, Cambridge, United Kingdom, 3 School of Biomedical Sciences, University of Nottingham Medical School, Queen’s Medical Centre, Nottingham, United Kingdom, 4 Schools of Biology and Electrical and Electronic Engineering, Institute of Biophysics, Imaging and Optical Science, University of Nottingham, Nottingham, United Kingdom 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