Research ArticleCalcium signaling

CRAC channels regulate astrocyte Ca2+ signaling and gliotransmitter release to modulate hippocampal GABAergic transmission

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Science Signaling  21 May 2019:
Vol. 12, Issue 582, eaaw5450
DOI: 10.1126/scisignal.aaw5450

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A CRAC team for astrocytes

Astrocytes are the most abundant glial cell type in the brain and release small molecules in a Ca2+-dependent fashion, such as ATP, that regulate neuronal excitability. Toth et al. found that Ca2+ release–activated Ca2+ (CRAC) channels comprising the Ca2+ sensor STIM1 and the Ca2+ channel Orai1 were a major route of Ca2+ entry into hippocampal astrocytes. Genetic ablation of either STIM1 or Orai1 in astrocytes decreased intracellular Ca2+ increases in response to the purinergic receptor agonists ATP or UTP or the protease-activated receptor agonist thrombin. Furthermore, astrocytes deficient in Orai1 showed reduced vesicle exocytosis and ATP release, as well as an inability to stimulate the excitability of hippocampal interneurons. These results suggest that enhancing CRAC channel activity in astrocytes could be a strategy to suppress neuronal excitability.

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