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

Activation of GABA receptors causes in immature neurons a functionally relevant decrease in the intracellular Cl concentration ([Cl ] ), a process termed ionic plasticity. Amount and duration of ionic plasticity depends on kinetic properties of [Cl ] homeostasis. In order to characterize the capacit...

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Bibliographic Details
Published in:Scientific reports 2020-10, Vol.10 (1), p.18399-18399, Article 18399
Main Authors: Kolbaev, Sergey N, Mohapatra, Namrata, Chen, Rongqing, Lombardi, Aniello, Staiger, Jochen F, Luhmann, Heiko J, Jedlicka, Peter, Kilb, Werner
Format: Article
Language:English
Subjects:
Animals
Brain slice preparation
Chloride transport
Chlorides - metabolism
gamma-Aminobutyric Acid - metabolism
Gramicidin
Hippocampus
Homeostasis
Pyramidal cells
Pyramidal Cells - metabolism
Rats
Solute Carrier Family 12, Member 2 - physiology
γ-Aminobutyric acid A receptors
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Summary:Activation of GABA receptors causes in immature neurons a functionally relevant decrease in the intracellular Cl concentration ([Cl ] ), a process termed ionic plasticity. Amount and duration of ionic plasticity depends on kinetic properties of [Cl ] homeostasis. In order to characterize the capacity of Cl accumulation and to quantify the effect of persistent GABAergic activity on [Cl ] , 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 ] 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 ] . Inhibition of tonic GABAergic currents induced a significant [Cl ] increase by 1.6 mM, while activation of tonic extrasynaptic GABA receptors with THIP significantly reduced [Cl ] . Simulations of neuronal [Cl ] homeostasis supported the observation, that basal levels of synaptic GABAergic activation do not affect [Cl ] . In summary, these results indicate that active Cl -uptake in immature hippocampal neurons is sufficient to maintain stable [Cl ] at basal levels of phasic and to some extent also to compensate tonic GABAergic activity.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-75382-1