title: TRPA1 channels regulate astrocyte resting calcium and inhibitory synapse efficacy through GAT-3.
abstract: Astrocytes contribute to the formation and function of synapses and are found throughout the brain, where they show intracellular store-mediated Ca(2+) signals. Here, using a membrane-tethered, genetically encoded calcium indicator (Lck-GCaMP3), we report the serendipitous discovery of a new type of Ca(2+) signal in rat hippocampal astrocyte-neuron cocultures. We found that Ca(2+) fluxes mediated by transient receptor potential A1 (TRPA1) channels gave rise to frequent and highly localized 'spotty' Ca(2+) microdomains near the membrane that contributed appreciably to resting Ca(2+) in astrocytes. Mechanistic evaluations in brain slices showed that decreases in astrocyte resting Ca(2+) concentrations mediated by TRPA1 channels decreased interneuron inhibitory synapse efficacy by reducing GABA transport by GAT-3, thus elevating extracellular GABA. Our data show how a transmembrane Ca(2+) source (TRPA1) targets a transporter (GAT-3) in astrocytes to regulate inhibitory synapses.
authors.affiliation: Department of Physiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
authors.forename: Eiji
authors.initials: E
authors.lastname: Shigetomi
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Tong
authors.forename: Kelvin Y
authors.initials: KY
authors.lastname: Kwan
authors.forename: David P
authors.initials: DP
authors.lastname: Corey
authors.forename: Baljit S
authors.initials: BS
authors.lastname: Khakh
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D050485:GABA Plasma Membrane Transport Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D051381:Rats; D013569:Synapses / Q000378:metabolism*; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D050485:GABA Plasma Membrane Transport Proteins; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat; D005680:gamma-Aminobutyric Acid; D002118:Calcium