KCC2 reverse mode helps to clear postsynaptically released potassium at glutamatergic synapses
Egor Byvaltcev, Mahraz Behbood, Jan‐Hendrik Schleimer, Thomas Gensch, Alexey Semyanov, Susanne Schreiber, Ulf Strauß
Abstract
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 I Kir 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 + .