TRPA1 channels regulate astrocyte resting calcium and inhibitory synapse efficacy through GAT-3

Nat Neurosci. 2011 Dec 11;15(1):70-80. doi: 10.1038/nn.3000.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Calcium / metabolism*
  • Cells, Cultured
  • Coculture Techniques
  • GABA Plasma Membrane Transport Proteins / metabolism*
  • Hippocampus / metabolism
  • Neurons / metabolism
  • Rats
  • Synapses / metabolism*
  • TRPA1 Cation Channel
  • TRPC Cation Channels / metabolism*
  • gamma-Aminobutyric Acid / metabolism


  • GABA Plasma Membrane Transport Proteins
  • TRPA1 Cation Channel
  • TRPC Cation Channels
  • Trpa1 protein, rat
  • gamma-Aminobutyric Acid
  • Calcium