title: Photolysis of caged Ca2+ but not receptor-mediated Ca2+ signaling triggers astrocytic glutamate release.
abstract: Astrocytes in hippocampal slices can dynamically regulate synaptic transmission in a process mediated by increases in intracellular Ca(2+). However, it is debated whether astrocytic Ca(2+) signals result in release of glutamate. We here compared astrocytic Ca(2+) signaling triggered by agonist exposure versus photolysis side by side. Using transgenic mice in which astrocytes selectively express the MrgA1 receptor, we found that receptor-mediated astrocytic Ca(2+) signaling consistently triggered neuronal hyperpolarization and decreased the frequency of miniature excitatory postsynaptic currents (EPSCs). In contrast, photolysis of caged Ca(2+) (o-nitrophenyl-EGTA) in astrocytes led to neuronal depolarization and increased the frequency of mEPSCs through a metabotropic glutamate receptor-mediated pathway. Analysis of transgenic mice in which astrocytic vesicular release is suppressed (dominant-negative SNARE mice) and pharmacological manipulations suggested that glutamate is primarily released by opening of anion channels rather than exocytosis. Combined, these studies show that photolysis but not by agonists induced astrocytic Ca(2+) signaling triggers glutamate release.
authors.affiliation: Center for Translational Neuromedicine, Division of Glia Disease and Therapeutics, University of Rochester Medical School, Rochester, New York 14642.
authors.forename: Fushun
authors.initials: F
authors.lastname: Wang
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Smith
authors.forename: Qiwu
authors.initials: Q
authors.lastname: Xu
authors.forename: Siri
authors.initials: S
authors.lastname: Goldman
authors.forename: Weiguo
authors.initials: W
authors.lastname: Peng
authors.forename: Jason H
authors.initials: JH
authors.lastname: Huang
authors.forename: Takahiro
authors.initials: T
authors.lastname: Takano
authors.forename: Maiken
authors.initials: M
authors.lastname: Nedergaard
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D020013:Calcium Signaling / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000235:genetics; D009924:Organ Culture Techniques; D010782:Photolysis; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D050600:SNARE Proteins / Q000172:deficiency / Q000235:genetics
chemical_list: C470191:MrgA1 protein, mouse; D043562:Receptors, G-Protein-Coupled; D050600:SNARE Proteins; D018698:Glutamic Acid