Autoren:	Lombardi, Aniello Jedlicka, Peter Luhmann, Heiko Kilb, Werner
Titel:	Interactions between membrane resistance, GABA-A receptor properties, bicarbonate dynamics and Cl<sup>−</sup> -transport shape activity-dependent changes of intracellular Cl<sup>−</sup> concentration
Online-Publikationsdatum:	8-Jul-2019
Erscheinungsdatum:	2019
Sprache des Dokuments:	Englisch
Zusammenfassung/Abstract:	The effects of ionotropic %26gamma;-aminobutyric acid receptor (GABA-A, GABAA) activation depends critically on the Cl−-gradient across neuronal membranes. Previous studies demonstrated that the intracellular Cl−-concentration ([Cl−]i) is not stable but shows a considerable amount of activity-dependent plasticity. To characterize how membrane properties and different molecules that are directly or indirectly involved in GABAergic synaptic transmission affect GABA-induced [Cl−]i changes, we performed compartmental modeling in the NEURON environment. These simulations demonstrate that GABA-induced [Cl−]i changes decrease at higher membrane resistance, revealing a sigmoidal dependency between both parameters. Increase in GABAergic conductivity enhances [Cl−]i with a logarithmic dependency, while increasing the decay time of GABAA receptors leads to a nearly linear enhancement of the [Cl−]i changes. Implementing physiological levels of HCO3−-conductivity to GABAA receptors enhances the [Cl−]i changes over a wide range of [Cl−]i, but this effect depends on the stability of the HCO3− gradient and the intracellular pH. Finally, these simulations show that pure diffusional Cl−-elimination from dendrites is slow and that a high activity of Cl−-transport is required to improve the spatiotemporal restriction of GABA-induced [Cl−]i changes. In summary, these simulations revealed a complex interplay between several key factors that influence GABA induced [Cl]i changes. The results suggest that some of these factors, including high resting [Cl−]i, high input resistance, slow decay time of GABAA receptors and dynamic HCO3− gradient, are specifically adapted in early postnatal neurons to facilitate limited activity dependent [Cl−]i decreases.
DDC-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-167
URN:	urn:nbn:de:hebis:77-publ-591355
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/4.0/
Zeitschrift:	International journal of molecular sciences 20 6
Seitenzahl oder Artikelnummer:	Art. 1416
Verlag:	Molecular Diversity Preservation International
Verlagsort:	Basel
Erscheinungsdatum:	2019
ISSN:	1422-0067
URL der Originalveröffentlichung:	http://dx.doi.org/10.3390/ijms20061416
DOI der Originalveröffentlichung:	10.3390/ijms20061416
Enthalten in den Sammlungen:	JGU-Publikationen