Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-167
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dc.contributor.authorLombardi, Aniello-
dc.contributor.authorJedlicka, Peter-
dc.contributor.authorLuhmann, Heiko-
dc.contributor.authorKilb, Werner-
dc.date.accessioned2019-07-08T11:24:07Z-
dc.date.available2019-07-08T13:24:07Z-
dc.date.issued2019-
dc.identifier.urihttps://openscience.ub.uni-mainz.de/handle/20.500.12030/169-
dc.description.abstractThe 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.en_GB
dc.description.sponsorshipDFG, Open Access-Publizieren Universität Mainz / Universitätsmedizin-
dc.language.isoeng-
dc.rightsCC BYde_DE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/-
dc.subject.ddc610 Medizinde_DE
dc.subject.ddc610 Medical sciencesen_GB
dc.titleInteractions between membrane resistance, GABA-A receptor properties, bicarbonate dynamics and Cl<sup>−</sup> -transport shape activity-dependent changes of intracellular Cl<sup>−</sup> concentrationen_GB
dc.typeZeitschriftenaufsatzde_DE
dc.identifier.urnurn:nbn:de:hebis:77-publ-591355-
dc.identifier.doihttp://doi.org/10.25358/openscience-167-
jgu.type.dinitypearticle-
jgu.type.versionPublished versionen_GB
jgu.type.resourceText-
jgu.organisation.departmentFB 04 Medizin-
jgu.organisation.number2700-
jgu.organisation.nameJohannes Gutenberg-Universität Mainz-
jgu.rights.accessrightsopenAccess-
jgu.journal.titleInternational journal of molecular sciences-
jgu.journal.volume20-
jgu.journal.issue6-
jgu.pages.alternativeArt. 1416-
jgu.publisher.year2019-
jgu.publisher.nameMolecular Diversity Preservation International-
jgu.publisher.placeBasel-
jgu.publisher.urihttp://dx.doi.org/10.3390/ijms20061416-
jgu.publisher.issn1422-0067-
jgu.organisation.placeMainz-
jgu.subject.ddccode610-
opus.date.accessioned2019-07-08T11:24:07Z-
opus.date.modified2020-03-16T11:29:15Z-
opus.date.available2019-07-08T13:24:07-
opus.subject.dfgcode00-000-
opus.organisation.stringFB 04: Medizin: Institut für Physiologiede_DE
opus.identifier.opusid59135-
opus.institute.number0477-
opus.metadataonlyfalse-
opus.type.contenttypeKeinede_DE
opus.type.contenttypeNoneen_GB
opus.affiliatedLuhmann, Heiko-
jgu.publisher.doi10.3390/ijms20061416
jgu.organisation.rorhttps://ror.org/023b0x485
Appears in collections:JGU-Publikationen

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