Glutamate transporter type 3 attenuates the activation of N-methyl-D-aspartate receptors co-expressed in Xenopus oocytes.
We studied the regulation of N-methy-D-aspartate receptor (NMDAR) current/activation by glutamate transporter type 3 (EAAT3), a neuronal EAAT in vivo, in the restricted extracellular space of a biological model. This model involved co-expressing EAAT3 and NMDAR (composed of NMDAR1-1a and NMDAR2A) in Xenopus oocytes. The NMDAR current was reduced in the co-expression oocytes but not in oocytes expressing NMDAR only when the flow of glutamate-containing superfusate was stopped. The degree of this current reduction was glutamate concentration-dependent. No reduction of NMDAR current was observed in Na+-free solution or when NMDA, a non-substrate for EAATs, was used as the agonist for NMDAR. In the continuous flow experiments, the dose-response curve of glutamate-induced current was shifted to the right-hand side in co-expression oocytes compared with oocytes expressing NMDAR alone. The degree of this shift depended on the abundance of EAAT3 in the co-expression oocytes. Thus, the glutamate concentrations sensed by NMDAR locally were lower than those in the superfusates. These results suggest that EAAT3 regulates the amplitude of NMDAR currents at pre-saturated concentrations of glutamate to EAAT3. Thus, EAATs, by rapidly regulating glutamate concentrations near NMDAR, modulate NMDAR current/activation.
Zuo
Zhiyi
Z
Department of Anesthesiology, University of Virginia Health System, Charlottesville, Virginia 22908-0710, USA. zz3c@virginia.edu
Fang
Hongyu
H
D027322:Amino Acid Transport System X-AG / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D015870:Gene Expression; D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000502:physiology; D005998:Glycine / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D016202:N-Methylaspartate / Q000502:physiology; D009865:Oocytes; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D027981:Symporters / Q000378:metabolism / Q000502:physiology*; D014982:Xenopus laevis
D027322:Amino Acid Transport System X-AG; D050491:Glutamate Plasma Membrane Transport Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D027981:Symporters; D018698:Glutamic Acid; D016202:N-Methylaspartate; D005998:Glycine