Charité - Universitätsmedizin Berlin, Institute of Cell- and Neurobiology, Charitéplatz 1, 10117 Berlin, Germany.
Institute for Theoretical Biology, Department of Biology, Humboldt-Universität zu Berlin, 10115 Berlin, Germany; Bernstein Center for Computational Neuroscience Berlin, 10115 Berlin, Germany.
Cell Rep. 2023 Aug 29;42(8):112934. doi: 10.1016/j.celrep.2023.112934. Epub 2023 Aug 1.
Extracellular potassium [K] 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 and K-sensitive electrodes as sensors of [K] as well as on in silico modeling, we demonstrate that the neuronal K-Cl co-transporter KCC2 clears local perisynaptic [K] 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], 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.
细胞外钾 [K] 在突触活动期间升高会逆行修饰突触前释放和星形胶质细胞摄取谷氨酸。因此，局部 K 清除和补充机制是谷氨酸能传递和可塑性的关键调节剂。基于对星形胶质细胞内向整流钾电流 I 和 K 敏感电极的记录，作为 [K] 的传感器，以及基于计算机建模，我们证明神经元 K-Cl 协同转运蛋白 KCC2 通过在活性依赖性反向模式下工作来清除局部突触周围 [K] 在突触兴奋期间。在反向模式下，KCC2 在树突棘中补充 K，补充 [K] 的清除，从而减弱突触前谷氨酸释放并缩短 LTP。因此，我们通过摄取突触后释放的 K 证明了 KCC2 在神经元-胶质细胞相互作用以及调节突触信号和可塑性中的生理作用。
