Abstract
Astrocytes contribute to the formation and function of synapses and are found throughout the brain where they display intracellular store mediated Ca2+ signals. Here, using a membrane tethered genetically encoded calcium indicator (Lck-GCaMP3), we report the serendipitous discovery of a novel Ca2+ signal in rat hippocampal astrocyte-neuron co-cultures. We found that TRPA1 channel mediated Ca2+ fluxes give rise to frequent and highly localised near membrane “spotty” Ca2+ microdomains that contribute significantly to resting Ca2+ levels of astrocytes. Mechanistic evaluations in brain slices show that decreasing astrocyte resting Ca2+ levels mediated by TRPA1 channels decreased interneuron inhibitory synapse efficacy by reducing GABA transport via GAT-3, thus elevating extracellular GABA levels. Our data indicate how a novel transmembrane Ca2+ source (TRPA1) targets a transporter (GAT-3) in astrocytes to regulate inhibitory synapses.
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