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Control of Glutamate Transport by Extracellular Potassium: Basis for a Negative Feedback on Synaptic Transmission

Rimmele, Theresa S. ; Rocher, Anne-Bérengère ; Wellbourne-Wood, Joel ; Chatton, Jean-Yves

In: Cerebral Cortex, 2017, vol. 27, no. 6, p. 3272-3283

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    Titre
    • Control of Glutamate Transport by Extracellular Potassium: Basis for a Negative Feedback on Synaptic Transmission
    Auteur
    • Rimmele, Theresa S.. Department of Fundamental Neurosciences, University of Lausanne, CH-1005 Lausanne, Switzerland
    • Rocher, Anne-Bérengère. Department of Fundamental Neurosciences, University of Lausanne, CH-1005 Lausanne, Switzerland
    • Wellbourne-Wood, Joel. Department of Fundamental Neurosciences, University of Lausanne, CH-1005 Lausanne, Switzerland
    • Chatton, Jean-Yves. Department of Fundamental Neurosciences, University of Lausanne, CH-1005 Lausanne, Switzerland
    Type de document
    • Postprint
    Langue
    • Inglese
    Publié dans
    • Cerebral Cortex, 2017, vol. 27, no. 6, p. 3272-3283. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:331830
    Summary
    Glutamate and K+, both released during neuronal firing, need to be tightly regulated to ensure accurate synaptic transmission. Extracellular glutamate and K+ ([K+]o) are rapidly taken up by glutamate transporters and K+-transporters or channels, respectively. Glutamate transport includes the exchange of one glutamate, 3 Na+, and one proton, in exchange for one K+. This K+ efflux allows the glutamate binding site to reorient in the outwardly facing position and start a new transport cycle. Here, we demonstrate the sensitivity of the transport process to [K+]o changes. Increasing [K+]o over the physiological range had an immediate and reversible inhibitory action on glutamate transporters. This K+-dependent transporter inhibition was revealed using microspectrofluorimetry in primary astrocytes, and whole-cell patch-clamp in acute brain slices and HEK293 cells expressing glutamate transporters. Previous studies demonstrated that pharmacological inhibition of glutamate transporters decreases neuronal transmission via extrasynaptic glutamate spillover and subsequent activation of metabotropic glutamate receptors (mGluRs). Here, we demonstrate that increasing [K+]o also causes a decrease in neuronal mEPSC frequency, which is prevented by group II mGluR inhibition. These findings highlight a novel, previously unreported physiological negative feedback mechanism in which [K+]o elevations inhibit glutamate transporters, unveiling a new mechanism for activity-dependent modulation of synaptic activity.