Translocation of glutamate transporter subtype excitatory amino acid carrier 1 protein in kainic acid-induced rat epilepsy.
Glutamate excitotoxicity has been implicated in the pathophysiology of epilepsy. Systemic injection of kainic acid (KA) in the rat produces an animal model of human temporal lobe epilepsy. We examined the temporal expression of the sodium-dependent neuronal glutamate transporter, excitatory amino acid carrier 1 (EAAC1), in KA-induced rat epilepsy. As an early alteration, perinuclear deposits of EAAC1 protein were found mainly in the large pyramidal neurons at the hippocampus, neocortex, piriform cortex, and amygdala with the reduction of neuropil staining 6 hours after KA injection. Immunoelectron microscopic study revealed that the perinuclear EAAC1 immunoreactivity corresponded to the translocation to the Golgi complex. At this time point, EAAC1 mRNA was down-regulated. The intracellular aggregation of EAAC1 primarily disappeared by 24 hours. In vitro studies indicated that internalization of EAAC1 from the plasma membrane to the intracellular compartment by KA treatment was associated with the reduction of electrogenic transporter currents. Our results suggest that the transient EAAC1 internalization participates in the modulation of the transporter function preventing excessive glutamate uptake to pyramidal neurons during the early stage of epilepsy.
Furuta
Akiko
A
Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. afuruta@ncnp.go.jp
Noda
Mami
M
Suzuki
Satoshi O
SO
Goto
Yoshinobu
Y
Kanahori
Yoshiko
Y
Rothstein
Jeffrey D
JD
Iwaki
Toru
T
D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007608:Kainic Acid; D008297:Male; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D027981:Symporters / Q000378:metabolism*
D027322:Amino Acid Transport System X-AG; D018690:Excitatory Amino Acid Agonists; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; C409466:NR1 NMDA receptor; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C493400:SLC1A1 protein, human; C493398:Slc1a1 protein, rat; D027981:Symporters; C104723:glutamate receptor ionotropic, AMPA 3; D018698:Glutamic Acid; C104722:glutamate receptor ionotropic, AMPA 2; D007608:Kainic Acid