A dynamic switch between inhibitory and excitatory currents in a neuronal glutamate transporter

摘要

Excitatory amino acid transporters (EAATs) terminate glutamatergic synaptic transmission and maintain extracellular glutamate concentrations in the central nervous system below excitotoxic levels. In addition to sustaining a secondary-active glutamate transport, EAAT glutamate transporters also function as anion-selective channels. Here, we report a gating process that makes anion channels associated with a neuronal glutamate transporter, EAAT4, permeable to cations and causes a selective increase of the open probability at voltages negative to the actual current reversal potential. The activation process depends on both membrane potential and extracellular glutamate concentration and causes an accumulation of EAAT4 anion channels in a state favoring cation influx and anion efflux. Gating of EAAT4 anion channels thus allows a switch between inhibitory currents in resting cells and excitatory currents in electrically active cells. This transporter-mediated conductance could modify the excitability of Purkinje neurons, providing them with an unprecedented mechanism for adaptation.