GABAergic Regulation of Astroglial Gliotransmission through Cx43 Hemichannels
Journal
International Journal of Molecular Sciences
ISSN
1422-0067
Date Issued
2022
Author(s)
Ivanka Jiménez-Dinamarca
Rachel Reyes-Lizana
Yordan Lemunao-Inostroza
Kevin Cárdenas
Raimundo Castro-Lazo
Claudia M. Lucero
Juan Prieto-Villalobos
Juan Andrés Orellana
Jimmy Stehberg
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:p>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.</jats:p>
Cite this document
Jiménez-Dinamarca, I., Reyes-Lizana, R., Lemunao-Inostroza, Y., Cárdenas, K., Castro-Lazo, R., Peña, F., Lucero, C. M., Prieto-Villalobos, J., Retamal, M. A., Orellana, J. A., & Stehberg, J. (2022). Gabaergic regulation of astroglial gliotransmission through cx43 hemichannels. International Journal of Molecular Sciences, 23(21), 13625. https://doi.org/10.3390/ijms232113625
Subjects
gaba
;
gaba(a) receptors
;
astrocytes
;
cx43 hemichannels
;
astroglia
;
connexin 43
;
gliotransmission
;
astroglial release