Dysfunction at glutamatergic synapses has been proposed as a mechanism in the development of neuropathic pain. Here we sought to determine whether peripheral nerve injury-induced neuropathic pain results in functional changes to primary afferent synapses. Signs of neuropathic pain as well as an induction of glial fibrillary acidic protein in immunostained spinal cord sections 4 days after parti...

Regulation of extracellular glutamate levels by muscarinic receptors in the striatum of unanesthetized rats was investigated by microdialysis. Extracellular glutamate levels were elevated by intrastriatal perfusion of L-trans-pyrrolidine-2,4-dicarboxylic acid (L-trans-PDC), a competitive substrate of plasma membrane excitatory amino acid transporters. The nonselective muscarinic agonist, oxotre...

Na(+)-dependent transporters for glutamate exist on astrocytes (EAAT1 and EAAT2) and neurons (EAAT3). These transporters presumably assist in keeping the glutamate concentration low in the extracellular fluid of brain. Recently, Na(+)-dependent glutamate transport was described on the abluminal membrane of the blood-brain barrier. To determine whether the above-mentioned transporters participat...

In the vertebrate brain, inhibition is largely mediated by γ-aminobutyric acid (GABA). This neurotransmitter comprises a signaling machinery of GABAA, GABAB receptors, transporters, glutamate decarboxylases (gads) and 4-aminobutyrate aminotransferase (abat), and associated proteins. Chloride is intimately related to GABAA receptor conductance, GABA uptake, and GADs activity. The response of tar...

Glutamate transporters in the central nervous system remove glutamate released from neurons to terminate the signal. These transporters localize to astrocyte process tips approaching neuronal synapses. The mechanisms underlying the localization of glutamate transporters to these processes, however, are not known. In this study, we demonstrate that the trimeric transmembrane transporter domain f...

L-Glutamic acid is a major excitatory neurotransmitter in the mammalian central nervous system. The termination of the glutamatergic transmission and the clearance of the excessive, neurotoxic concentrations of glutamate is ensured by a high affinity glutamate uptake system. Four homologous types of Na/K-dependent high affinity glutamate transporters, glutamate/aspartate transporter, glutamate ...

Glutamate and aspartate play dual roles in the central nervous system as essential amino acids and the principal excitatory neurotransmitters. The theory of excitotoxicity presents the paradoxical view that these excitatory amino acids may also become endogenous neurotoxins any time the brain’s energy homeostasis is compromised (16,23,42,59). Cerebral ischemia and traumatic brain injury result ...