GABAergic Regulation of Astroglial Gliotransmission through Cx43 Hemichannels
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<sup>-</sup> via the GABA<sub>A</sub> receptor or efflux or K<sup>+</sup>...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/21/13625 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ivanka Jiménez-Dinamarca |
| collection | DOAJ |
| description | 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<sup>-</sup> via the GABA<sub>A</sub> receptor or efflux or K<sup>+</sup> via the GABA<sub>B</sub> receptor, inducing hyperpolarization and synaptic inhibition. In astrocytes, the activation of both GABA<sub>A</sub> and GABA<sub>B</sub> receptors induces an increase in intracellular Ca<sup>2+</sup> and the release of glutamate and ATP. Connexin 43 (Cx43) hemichannels are among the main Ca<sup>2+</sup>-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<sup>2+</sup>-dependent increase in Cx43 hemichannel activity in astrocytes mediated by the GABA<sub>A</sub> receptor, as it was blunted by the GABA<sub>A</sub> receptor antagonist bicuculline but unaffected by GABA<sub>B</sub> 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. |
| first_indexed | 2024-03-09T18:59:19Z |
| format | Article |
| id | doaj.art-1eb39fad6cc946ea97c563f00249151e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T18:59:19Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1eb39fad6cc946ea97c563f00249151e2023-11-24T05:11:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123211362510.3390/ijms232113625GABAergic Regulation of Astroglial Gliotransmission through Cx43 HemichannelsIvanka Jiménez-Dinamarca0Rachel Reyes-Lizana1Yordan Lemunao-Inostroza2Kevin Cárdenas3Raimundo Castro-Lazo4Francisca Peña5Claudia M. Lucero6Juan Prieto-Villalobos7Mauricio Antonio Retamal8Juan Andrés Orellana9Jimmy Stehberg10Laboratorio de Neurobiología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad Andres Bello, Santiago 8370186, ChileLaboratorio de Neurobiología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad Andres Bello, Santiago 8370186, ChileLaboratorio de Neurobiología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad Andres Bello, Santiago 8370186, ChileLaboratorio de Neurobiología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad Andres Bello, Santiago 8370186, ChileLaboratorio de Neurobiología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad Andres Bello, Santiago 8370186, ChileLaboratorio de Neurobiología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad Andres Bello, Santiago 8370186, ChileDepartamento de Neurología, Escuela de Medicina and Centro Interdisciplinario de Neurociencias, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago 8330024, ChileDepartamento de Neurología, Escuela de Medicina and Centro Interdisciplinario de Neurociencias, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago 8330024, ChileCentro de Fisiología Celular e Integrativa, Facultad de Medicina, Universidad del Desarrollo–Clínica Alemana, Santiago 7780272, ChileDepartamento de Neurología, Escuela de Medicina and Centro Interdisciplinario de Neurociencias, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago 8330024, ChileLaboratorio de Neurobiología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad Andres Bello, Santiago 8370186, ChileGamma-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<sup>-</sup> via the GABA<sub>A</sub> receptor or efflux or K<sup>+</sup> via the GABA<sub>B</sub> receptor, inducing hyperpolarization and synaptic inhibition. In astrocytes, the activation of both GABA<sub>A</sub> and GABA<sub>B</sub> receptors induces an increase in intracellular Ca<sup>2+</sup> and the release of glutamate and ATP. Connexin 43 (Cx43) hemichannels are among the main Ca<sup>2+</sup>-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<sup>2+</sup>-dependent increase in Cx43 hemichannel activity in astrocytes mediated by the GABA<sub>A</sub> receptor, as it was blunted by the GABA<sub>A</sub> receptor antagonist bicuculline but unaffected by GABA<sub>B</sub> 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.https://www.mdpi.com/1422-0067/23/21/13625GABAGABA<sub>A</sub> receptorsastrocytesCx43 hemichannelsastrogliaconnexin 43 |
| spellingShingle | 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 GABAergic Regulation of Astroglial Gliotransmission through Cx43 Hemichannels International Journal of Molecular Sciences GABA GABA<sub>A</sub> receptors astrocytes Cx43 hemichannels astroglia connexin 43 |
| title | GABAergic Regulation of Astroglial Gliotransmission through Cx43 Hemichannels |
| title_full | GABAergic Regulation of Astroglial Gliotransmission through Cx43 Hemichannels |
| title_fullStr | GABAergic Regulation of Astroglial Gliotransmission through Cx43 Hemichannels |
| title_full_unstemmed | GABAergic Regulation of Astroglial Gliotransmission through Cx43 Hemichannels |
| title_short | GABAergic Regulation of Astroglial Gliotransmission through Cx43 Hemichannels |
| title_sort | gabaergic regulation of astroglial gliotransmission through cx43 hemichannels |
| topic | GABA GABA<sub>A</sub> receptors astrocytes Cx43 hemichannels astroglia connexin 43 |
| url | https://www.mdpi.com/1422-0067/23/21/13625 |
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