K+ efflux through postsynaptic NMDA receptors suppresses local astrocytic glutamate uptake. Issue 5 (27th January 2022)

• Record Type: Journal Article
• Authors: Tyurikova, Olga; Shih, Pei‐Yu; Dembitskaya, Yulia; Savtchenko, Leonid P.; McHugh, Thomas J.; Rusakov, Dmitri A.; Semyanov, Alexey
• Is Part Of: Glia. Volume 70:Issue 5(2022)
• Page Start: 961
• Page End: 974
• Publication Date: 2022-01-27
• Subjects: astrocyte -- depolarization -- glutamate uptake -- NMDA receptor -- potassium -- spillover; Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.24150
• Languages: English
• ISSNs: 0894-1491

Abstract

Abstract: Glutamatergic transmission prompts K + efflux through postsynaptic NMDA receptors. The ensuing hotspot of extracellular K + elevation depolarizes presynaptic terminal, boosting glutamate release, but whether this also affects glutamate uptake in local astroglia has remained an intriguing question. Here, we find that the pharmacological blockade, or conditional knockout, of postsynaptic NMDA receptors suppresses use‐dependent increase in the amplitude and duration of the astrocytic glutamate transporter current (IGluT ), whereas blocking astrocytic K + channels prevents the duration increase only. Glutamate spot‐uncaging reveals that astrocyte depolarization, rather than extracellular K + rises per se, is required to reduce the amplitude and duration of IGluT . Biophysical simulations confirm that local transient elevations of extracellular K + can inhibit local glutamate uptake in fine astrocytic processes. Optical glutamate sensor imaging and a two‐pathway test relate postsynaptic K + efflux to enhanced extrasynaptic glutamate signaling. Thus, repetitive glutamatergic transmission triggers a feedback loop in which postsynaptic K + efflux can transiently facilitate presynaptic release while reducing local glutamate uptake. Main Points: Potassium efflux through postsynaptic NMDA receptors depolarizes perisynaptic astroglia. Potassium‐mediated depolarization reduces astrocytic glutamate uptake. Reduced uptake boosts glutamate spillover actions.