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Authors: Lombardi, Aniello
Jedlicka, Peter
Luhmann, Heiko
Kilb, Werner
Title: 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 publication date: 8-Jul-2019
Year of first publication: 2019
Language: english
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: 610 Medizin
610 Medical sciences
Institution: Johannes Gutenberg-Universität Mainz
Department: FB 04 Medizin
Place: Mainz
URN: urn:nbn:de:hebis:77-publ-591355
Version: Published version
Publication type: Zeitschriftenaufsatz
License: CC BY
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Journal: International journal of molecular sciences
Pages or article number: Art. 1416
Publisher: Molecular Diversity Preservation International
Publisher place: Basel
Issue date: 2019
ISSN: 1422-0067
Publisher URL:
Publisher DOI: 10.3390/ijms20061416
Appears in collections:JGU-Publikationen

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