GABAergic Regulation of Astroglial Gliotransmission through Cx43 Hemichannels.

Autor: Jiménez-Dinamarca I; Laboratorio de Neurobiología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad Andres Bello, Santiago 8370186, Chile., Reyes-Lizana R; Laboratorio de Neurobiología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad Andres Bello, Santiago 8370186, Chile., Lemunao-Inostroza Y; Laboratorio de Neurobiología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad Andres Bello, Santiago 8370186, Chile., Cárdenas K; Laboratorio de Neurobiología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad Andres Bello, Santiago 8370186, Chile., Castro-Lazo R; Laboratorio de Neurobiología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad Andres Bello, Santiago 8370186, Chile., Peña F; Laboratorio de Neurobiología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad Andres Bello, Santiago 8370186, Chile.; Centro de Fisiología Celular e Integrativa, Facultad de Medicina, Universidad del Desarrollo-Clínica Alemana, Santiago 7780272, Chile., Lucero CM; Departamento de Neurología, Escuela de Medicina and Centro Interdisciplinario de Neurociencias, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile., Prieto-Villalobos J; Departamento de Neurología, Escuela de Medicina and Centro Interdisciplinario de Neurociencias, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile., Retamal MA; Centro de Fisiología Celular e Integrativa, Facultad de Medicina, Universidad del Desarrollo-Clínica Alemana, Santiago 7780272, Chile., Orellana JA; Departamento de Neurología, Escuela de Medicina and Centro Interdisciplinario de Neurociencias, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile., Stehberg J; Laboratorio de Neurobiología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad Andres Bello, Santiago 8370186, Chile.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2022 Nov 07; Vol. 23 (21). Date of Electronic Publication: 2022 Nov 07.
DOI: 10.3390/ijms232113625
Abstrakt: 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 GABA A receptor or efflux or K + via the GABA B receptor, inducing hyperpolarization and synaptic inhibition. In astrocytes, the activation of both GABA A and GABA B receptors induces an increase in intracellular Ca 2+ and the release of glutamate and ATP. Connexin 43 (Cx43) hemichannels are among the main Ca 2+ -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 Ca 2+ -dependent increase in Cx43 hemichannel activity in astrocytes mediated by the GABA A receptor, as it was blunted by the GABA A receptor antagonist bicuculline but unaffected by GABA B 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.
Databáze: MEDLINE
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