When Are Depolarizing GABAergic Responses Excitatory?

The membrane responses upon activation of GABA(A) receptors critically depend on the intracellular Cl− concentration ([Cl−]i), which is maintained by a set of transmembrane transporters for Cl−. During neuronal development, but also under several pathophysiological conditions, the prevailing express...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autor principal:	Werner Kilb
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	chloride homeostasis NKCC1 KCC2 SLC12A2 SLC12A5 gaba receptor Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/6374fa11077c4d9e8df3889480f8f7ef
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6374fa11077c4d9e8df3889480f8f7ef
record_format	dspace
spelling	oai:doaj.org-article:6374fa11077c4d9e8df3889480f8f7ef2021-11-30T16:53:58ZWhen Are Depolarizing GABAergic Responses Excitatory?1662-509910.3389/fnmol.2021.747835https://doaj.org/article/6374fa11077c4d9e8df3889480f8f7ef2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnmol.2021.747835/fullhttps://doaj.org/toc/1662-5099The membrane responses upon activation of GABA(A) receptors critically depend on the intracellular Cl− concentration ([Cl−]i), which is maintained by a set of transmembrane transporters for Cl−. During neuronal development, but also under several pathophysiological conditions, the prevailing expression of the Cl− loader NKCC1 and the low expression of the Cl− extruder KCC2 causes elevated [Cl−]i, which result in depolarizing GABAergic membrane responses. However, depolarizing GABAergic responses are not necessarily excitatory, as GABA(A) receptors also reduces the input resistance of neurons and thereby shunt excitatory inputs. To summarize our knowledge on the effect of depolarizing GABA responses on neuronal excitability, this review discusses theoretical considerations and experimental studies illustrating the relation between GABA conductances, GABA reversal potential and neuronal excitability. In addition, evidences for the complex spatiotemporal interaction between depolarizing GABAergic and glutamatergic inputs are described. Moreover, mechanisms that influence [Cl−]i beyond the expression of Cl− transporters are presented. And finally, several in vitro and in vivo studies that directly investigated whether GABA mediates excitation or inhibition during early developmental stages are summarized. In summary, these theoretical considerations and experimental evidences suggest that GABA can act as inhibitory neurotransmitter even under conditions that maintain substantial depolarizing membrane responses.Werner KilbFrontiers Media S.A.articlechloride homeostasisNKCC1KCC2SLC12A2SLC12A5gaba receptorNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Molecular Neuroscience, Vol 14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	chloride homeostasis NKCC1 KCC2 SLC12A2 SLC12A5 gaba receptor Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	chloride homeostasis NKCC1 KCC2 SLC12A2 SLC12A5 gaba receptor Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Werner Kilb When Are Depolarizing GABAergic Responses Excitatory?
description	The membrane responses upon activation of GABA(A) receptors critically depend on the intracellular Cl− concentration ([Cl−]i), which is maintained by a set of transmembrane transporters for Cl−. During neuronal development, but also under several pathophysiological conditions, the prevailing expression of the Cl− loader NKCC1 and the low expression of the Cl− extruder KCC2 causes elevated [Cl−]i, which result in depolarizing GABAergic membrane responses. However, depolarizing GABAergic responses are not necessarily excitatory, as GABA(A) receptors also reduces the input resistance of neurons and thereby shunt excitatory inputs. To summarize our knowledge on the effect of depolarizing GABA responses on neuronal excitability, this review discusses theoretical considerations and experimental studies illustrating the relation between GABA conductances, GABA reversal potential and neuronal excitability. In addition, evidences for the complex spatiotemporal interaction between depolarizing GABAergic and glutamatergic inputs are described. Moreover, mechanisms that influence [Cl−]i beyond the expression of Cl− transporters are presented. And finally, several in vitro and in vivo studies that directly investigated whether GABA mediates excitation or inhibition during early developmental stages are summarized. In summary, these theoretical considerations and experimental evidences suggest that GABA can act as inhibitory neurotransmitter even under conditions that maintain substantial depolarizing membrane responses.
format	article
author	Werner Kilb
author_facet	Werner Kilb
author_sort	Werner Kilb
title	When Are Depolarizing GABAergic Responses Excitatory?
title_short	When Are Depolarizing GABAergic Responses Excitatory?
title_full	When Are Depolarizing GABAergic Responses Excitatory?
title_fullStr	When Are Depolarizing GABAergic Responses Excitatory?
title_full_unstemmed	When Are Depolarizing GABAergic Responses Excitatory?
title_sort	when are depolarizing gabaergic responses excitatory?
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6374fa11077c4d9e8df3889480f8f7ef
work_keys_str_mv	AT wernerkilb whenaredepolarizinggabaergicresponsesexcitatory
_version_	1718406447581102080

When Are Depolarizing GABAergic Responses Excitatory?

Ejemplares similares