These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Modification of epileptiform discharges in neocortical neurons following glutamate uptake inhibition.
    Author: Campbell S, Hablitz JJ.
    Journal: Epilepsia; 2005; 46 Suppl 5():129-33. PubMed ID: 15987267.
    Abstract:
    Sodium-dependent high-affinity glutamate transporters regulate synaptic glutamate levels to maintain low ambient levels of glutamate and prevent excitotoxicity. Most studies using pharmacological inhibition of glutamate transport to examine the involvement of glutamate transporters in regulating synaptic activity have examined small synaptic currents. Using in vitro brain slices, we investigated the effects of uptake inhibition on two types of epileptiform activity, bicuculline-induced paroxysmal activity, and epileptiform responses in the freeze-lesion epilepsy model. In layer II/III pyramidal cells of the prefrontal cortex, inhibiting uptake with low concentrations of DL-threo-ss-benzyloxyaspartic acid (TBOA) (20 or 30 microM) prolonged bicuculline-induced epileptiform activity. At higher concentrations, TBOA (150 or 300 microM) caused a transient enhancement of epileptiform discharges that was followed by a decrease. In the freeze-lesion model, inhibiting uptake also increased the amplitude and response area of evoked activity. The prolongation of epileptiform activity exhibited by the inhibition of glutamate uptake (TBOA 20 or 30 microM) is attributed to an increase in the level of glutamate extracellularly during uptake blockade, resulting in sustained activation of glutamate receptors. The decrease in epileptiform activity at higher TBOA concentration could be due to glutamate receptor desensitization or loss of excitability due to a depolarization block. The present results suggest that decreases in glutamate uptake can be proconvulsant in the two models of epilepsy examined.
    [Abstract] [Full Text] [Related] [New Search]