Arachidonic acid activates a proton current in the rat glutamate transporter EAAT4.
The excitatory amino acid transporter EAAT4 is expressed predominantly in Purkinje neurons in the rat cerebellum (1-3), and it participates in postsynaptic reuptake of glutamate released at the climbing fiber synapse (4). 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 (5). 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.
Tzingounis
A V
AV
Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201, USA.
Lin
C L
CL
Rothstein
J D
JD
Kavanaugh
M P
MP
D027322:Amino Acid Transport System X-AG; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D050581:Excitatory Amino Acid Transporter 4; D050491:Glutamate Plasma Membrane Transport Proteins; D011522:Protons; D011689:Purkinje Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017470:Receptors, Glutamate / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D027981:Symporters; D014981:Xenopus
D027322:Amino Acid Transport System X-AG; D050581:Excitatory Amino Acid Transporter 4; D050491:Glutamate Plasma Membrane Transport Proteins; D011522:Protons; D017470:Receptors, Glutamate; D011994:Recombinant Proteins; C493389:Slc1a6 protein, rat; D027981:Symporters; D016718:Arachidonic Acid