Details

Autor(en) / Beteiligte

• Byvaltcev, Egor
• Behbood, Mahraz
• Schleimer, Jan-Hendrik
• Gensch, Thomas
• Semyanov, Alexey
• Schreiber, Susanne
• Strauss, Ulf

Titel

KCC2 reverse mode helps to clear postsynaptically released potassium at glutamatergic synapses

Ist Teil von

• Cell reports (Cambridge), 2023-08, Vol.42 (8), p.112934-112934, Article 112934

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• Extracellular potassium [K+]o elevation during synaptic activity retrogradely modifies presynaptic release and astrocytic uptake of glutamate. Hence, local K+ clearance and replenishment mechanisms are crucial regulators of glutamatergic transmission and plasticity. Based on recordings of astrocytic inward rectifier potassium current IKir and K+-sensitive electrodes as sensors of [K+]o as well as on in silico modeling, we demonstrate that the neuronal K+-Cl- co-transporter KCC2 clears local perisynaptic [K+]o during synaptic excitation by operating in an activity-dependent reversed mode. In reverse mode, KCC2 replenishes K+ in dendritic spines and complements clearance of [K+]o, therewith attenuating presynaptic glutamate release and shortening LTP. We thus demonstrate a physiological role of KCC2 in neuron-glial interactions and regulation of synaptic signaling and plasticity through the uptake of postsynaptically released K+. [Display omitted] •KCC2 is recruited upon perisynaptic K+ increase due to glutamatergic synaptic activity•In reverse mode, KCC2 transiently transports perisynaptic K+ back intothe spine•KCC2 reversal diminishes perisynaptic K+, especially when astrocytic K+ uptake is impaired•KCC2 reverse mode temporarily restricts presynaptic glutamate release and attenuates LTP Byvaltcev et al. demonstrate a physiological role of KCC2 at dendritic spines by showing KCC2 operation in reverse mode that restricts the perisynaptic potassium increase upon glutamatergic stimulation. They describe KCC2 interactions with other perisynaptic potassium transport mechanisms and the consequences of KCC2 modifications for synaptic signaling.