J Biol Chem, Vol. 273, Issue 28, 17315-17317, July 10, 1998

COMMUNICATION
Arachidonic Acid Activates a Proton Current in the Rat Glutamate Transporter EAAT4

Anastassios V. Tzingounis, Chien-Liang Lin^§, Jeffrey D. Rothstein^§, and Michael P. Kavanaugh

From the  Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201 and the ^§ Department of Neurology, The Johns Hopkins University, Baltimore, Maryland 21205

The excitatory amino acid transporter EAAT4 is expressed predominantly in Purkinje neurons in the rat cerebellum (), and it participates in postsynaptic reuptake of glutamate released at the climbing fiber synapse (). Transporter-mediated currents in Purkinje neurons are increased more than 3-fold by arachidonic acid, a second messenger that is liberated following depolarization-induced Ca²⁺ activation of phospholipase A₂ (). In this study we demonstrate that application of arachidonic acid to oocytes expressing rat EAAT4 increased glutamate-induced currents to a similar extent. However, arachidonic acid did not cause an increase in the rate of glutamate transport or in the chloride current associated with glutamate transport but rather activated a proton-selective conductance. These data reveal a novel action of arachidonate on a glutamate transporter and suggest a mechanism by which synaptic activity may decrease intracellular pH in neurons where this transporter is localized.