GABAergic Regulation of Astroglial Gliotransmission through Cx43 Hemichannels

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dc.article.number13625
dc.catalogadorgjm
dc.contributor.authorJimenez-Dinamarca, Ivanka
dc.contributor.authorReyes-Lizana, Rachel
dc.contributor.authorLemunao-Inostroza, Yordan
dc.contributor.authorCardenas, Kevin
dc.contributor.authorCastro-Lazo, Raimundo
dc.contributor.authorPeña, Francisca
dc.contributor.authorLucero, Claudia M.
dc.contributor.authorPrieto Villalobos, Juan Carlos
dc.contributor.authorRetamal, Mauricio Antonio
dc.contributor.authorOrellana Roca, Juan Andrés
dc.contributor.authorStehberg, Jimmy
dc.date.accessioned2024-10-16T15:10:20Z
dc.date.available2024-10-16T15:10:20Z
dc.date.issued2022
dc.description.abstractGamma-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 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 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.
dc.fechaingreso.objetodigital2024-10-16
dc.format.extent15 páginas
dc.fuente.origenORCID
dc.identifier.doi10.3390/ijms232113625
dc.identifier.eissn1422-0067
dc.identifier.urihttps://doi.org/10.3390/ijms232113625
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/88259
dc.identifier.wosidWOS:000883885600001
dc.information.autorucEscuela de Medicina; Prieto Villalobos, Juan Carlos; S/I; 1071673
dc.information.autorucEscuela de Medicina; Orellana Roca, Juan Andrés; 0000-0003-4076-207X; 126007
dc.issue.numero21
dc.language.isoen
dc.nota.accesocontenido completo
dc.revistaInternational Journal of Molecular Sciences
dc.rightsacceso abierto
dc.rights.licenseCC BY 4.0 Attribution 4.0 International Deed
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectGABA
dc.subjectGABA(A) receptors
dc.subjectAstrocytes
dc.subjectCx43 hemichannels
dc.subjectAstroglia
dc.subjectConnexin 43
dc.subjectGliotransmission
dc.subjectAstroglial release
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleGABAergic Regulation of Astroglial Gliotransmission through Cx43 Hemichannels
dc.typeartículo
dc.volumen23
sipa.codpersvinculados1071673
sipa.codpersvinculados126007
sipa.trazabilidadORCID;2024-10-14
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