Niflumic Acid Activates Additional Currents of the Human Glial L-Glutamate Transporter EAAT1 in a Substrate-Dependent Manner

Abstract

The astrocytic L-glutamate (L-Glu) transporter EAAT1 participates in the removal of L-Glu from the synaptic cleft and maintenance of non-toxic concentrations in the extracellular fluid. We have shown that niflumic acid (NFA), a non-steroidal anti-inflammatory drug (NSAIDs), alters L-Glu-induced EAAT1 currents in a voltage-dependent manner using the two-electrode voltage clamp technique in Xenopus oocytes expressing EAAT1. In this study, we characterised the effects of NFA on each type of ion-flux through EAAT1. NFA modulated currents induced by both L-Glu and L-aspartate (L-Asp) in a voltage-dependent manner. Ion-substitution experiments revealed that the activation of additional H⁺ conductance was involved in the modulation of currents induced by L-Asp and L-Glu, but Cl⁻ was involved only with the L-Asp currents. NFA activated additional currents of EAAT1 in a substrate-dependent manner.