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http://doi.org/10.25358/openscience-5757
Autoren: | Kolbaev, Sergey N. Mohapatra, Namrata Chen, Rongqing Lombardi, Aniello Staiger, Jochen F. Luhmann, Heiko J. Jedlicka, Peter Kilb, Werner |
Titel: | NKCC-1 mediated Cl− uptake in immature CA3 pyramidal neurons is sufficient to compensate phasic GABAergic inputs |
Online-Publikationsdatum: | 22-Apr-2021 |
Erscheinungsdatum: | 2020 |
Sprache des Dokuments: | Englisch |
Zusammenfassung/Abstract: | Activation of GABAA receptors causes in immature neurons a functionally relevant decrease in the intracellular Cl− concentration ([Cl−]i), a process termed ionic plasticity. Amount and duration of ionic plasticity depends on kinetic properties of [Cl−]i homeostasis. In order to characterize the capacity of Cl− accumulation and to quantify the effect of persistent GABAergic activity on [Cl−]i, we performed gramicidin-perforated patch-clamp recordings from CA3 pyramidal neurons of immature (postnatal day 4–7) rat hippocampal slices. These experiments revealed that inhibition of NKCC1 decreased [Cl−]i toward passive distribution with a time constant of 381 s. In contrast, active Cl− accumulation occurred with a time constant of 155 s, corresponding to a rate of 15.4 µM/s. Inhibition of phasic GABAergic activity had no significant effect on steady state [Cl−]i. Inhibition of tonic GABAergic currents induced a significant [Cl−]i increase by 1.6 mM, while activation of tonic extrasynaptic GABAA receptors with THIP significantly reduced [Cl−]i.. Simulations of neuronal [Cl−]i homeostasis supported the observation, that basal levels of synaptic GABAergic activation do not affect [Cl−]i. In summary, these results indicate that active Cl−-uptake in immature hippocampal neurons is sufficient to maintain stable [Cl−]i at basal levels of phasic and to some extent also to compensate tonic GABAergic activity. |
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-5757 |
Version: | Published version |
Publikationstyp: | Zeitschriftenaufsatz |
Nutzungsrechte: | CC BY |
Informationen zu den Nutzungsrechten: | https://creativecommons.org/licenses/by/4.0/ |
Zeitschrift: | Scientific reports 10 |
Seitenzahl oder Artikelnummer: | 18399 |
Verlag: | Macmillan Publishers Limited, part of Springer Nature |
Verlagsort: | London |
Erscheinungsdatum: | 2020 |
ISSN: | 2045-2322 |
URL der Originalveröffentlichung: | https://doi.org/10.1038/s41598-020-75382-1 |
DOI der Originalveröffentlichung: | 10.1038/s41598-020-75382-1 |
Enthalten in den Sammlungen: | JGU-Publikationen |
Dateien zu dieser Ressource:
Datei | Beschreibung | Größe | Format | ||
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kolbaev_sergey_n.-nkcc-1_mediate-20210419123730643.pdf | 1.94 MB | Adobe PDF | Öffnen/Anzeigen |