Arachidonic acid elicits a substrate-gated proton current associated with the glutamate transporter EAAT4

Arachidonic acid modulates both electrical and biochemical properties of membrane proteins involved in cellular signaling. In Xenopus laevis oocytes expressing the excitatory amino acid transporter EAAT4, physiologically relevant concentrations of arachidonic acid increase the amplitude of the substrate-activated current by roughly twofold at -60 mV. This stimulation is not attributable to the modulation of either substrate/ion cotransport or the ligand-gated chloride current, the major conductance associated with this carrier. Ion-substitution experiments reveal that arachidonic acid stimulates a proton-selective conductance. The effect does not require metabolism of arachidonic acid and is not blocked by inhibitors of endogenous oocyte ion-exchangers. This proton conductance expands the complex repertoire of the ligand-gated channel properties associated with EAAT4.