NKCC-1 mediated Cl− uptake in immature CA3 pyramidal neurons is sufficient to compensate phasic GABAergic inputs

2020 | journal article. A publication with affiliation to the University of Göttingen.

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​NKCC-1 mediated Cl− uptake in immature CA3 pyramidal neurons is sufficient to compensate phasic GABAergic inputs​
Kolbaev, S. N.; Mohapatra, N.; Chen, R.; Lombardi, A.; Staiger, J. F. ; Luhmann, H. J. & Jedlicka, P. et al.​ (2020) 
Scientific Reports10(1).​ DOI: https://doi.org/10.1038/s41598-020-75382-1 

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Authors
Kolbaev, Sergey N.; Mohapatra, Namrata; Chen, Rongqing; Lombardi, Aniello; Staiger, Jochen F. ; Luhmann, Heiko J.; Jedlicka, Peter; Kilb, Werner
Abstract
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.
Issue Date
2020
Journal
Scientific Reports 
eISSN
2045-2322
Language
English
Sponsor
Deutsche Forschungsgemeinschaft
Bundesministerium für Bildung und Forschung
Projekt DEAL

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