GABAergic Regulation of Astroglial Gliotransmission through Cx43 Hemichannels

Ivanka Jiménez-Dinamarca, Rachel Reyes-Lizana, Yordan Lemunao-Inostroza, Kevin Cárdenas, Raimundo Castro-Lazo, Francisca Peña, Claudia M. Lucero, Juan Prieto-Villalobos, Mauricio Antonio Retamal, Juan Andrés Orellana, Jimmy Stehberg

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Gamma-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain. It is produced by interneurons and recycled by astrocytes. In neurons, GABA activates the influx of Cl- via the GABAA receptor or efflux or K+ via the GABAB receptor, inducing hyperpolarization and synaptic inhibition. In astrocytes, the activation of both GABAA and GABAB receptors induces an increase in intracellular Ca2+ and the release of glutamate and ATP. Connexin 43 (Cx43) hemichannels are among the main Ca2+-dependent cellular mechanisms for the astroglial release of glutamate and ATP. However, no study has evaluated the effect of GABA on astroglial Cx43 hemichannel activity and Cx43 hemichannel-mediated gliotransmission. Here we assessed the effects of GABA on Cx43 hemichannel activity in DI NCT1 rat astrocytes and hippocampal brain slices. We found that GABA induces a Ca2+-dependent increase in Cx43 hemichannel activity in astrocytes mediated by the GABAA receptor, as it was blunted by the GABAA receptor antagonist bicuculline but unaffected by GABAB receptor antagonist CGP55845. Moreover, GABA induced the Cx43 hemichannel-dependent release of glutamate and ATP, which was also prevented by bicuculline, but unaffected by CGP. Gliotransmission in response to GABA was also unaffected by pannexin 1 channel blockade. These results are discussed in terms of the possible role of astroglial Cx43 hemichannel-mediated glutamate and ATP release in regulating the excitatory/inhibitory balance in the brain and their possible contribution to psychiatric disorders.

Original languageEnglish
Article number13625
JournalInternational Journal of Molecular Sciences
Volume23
Issue number21
DOIs
Publication statusPublished - Nov 2022

Keywords

  • astrocytes
  • astroglia
  • astroglial release
  • connexin 43
  • Cx43 hemichannels
  • GABA
  • GABA receptors
  • gliotransmission

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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