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
Affiliations
Egor Byvaltcev
Charité - Universitätsmedizin Berlin, Institute of Cell- and Neurobiology, Charitéplatz 1, 10117 Berlin, Germany
Mahraz Behbood
Institute for Theoretical Biology, Department of Biology, Humboldt-Universität zu Berlin, 10115 Berlin, Germany; Bernstein Center for Computational Neuroscience Berlin, 10115 Berlin, Germany
Jan-Hendrik Schleimer
Institute for Theoretical Biology, Department of Biology, Humboldt-Universität zu Berlin, 10115 Berlin, Germany; Bernstein Center for Computational Neuroscience Berlin, 10115 Berlin, Germany
Thomas Gensch
Institute of Biological Information Processing 1 (IBI-1, Molecular and Cellular Physiology), Forschungszentrum Jülich, Wilhem-Jonen Straße, 52428 Jülich, Germany
Alexey Semyanov
Department of Physiology, Jiaxing University College of Medicine, Zhejiang Pro, Jiaxing 314033, China
Susanne Schreiber
Institute for Theoretical Biology, Department of Biology, Humboldt-Universität zu Berlin, 10115 Berlin, Germany; Bernstein Center for Computational Neuroscience Berlin, 10115 Berlin, Germany
Ulf Strauss
Charité - Universitätsmedizin Berlin, Institute of Cell- and Neurobiology, Charitéplatz 1, 10117 Berlin, Germany; Corresponding author
Summary: 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+.
