Plasticity of excitatory amino acid transporters in experimental epilepsy.

Abstract

PURPOSE:

To examine the relationship between seizures and excitatory amino acid transporter (EAAT) activity and whether up-regulation of EAAT activity alters epileptogenicity.

METHODS:

In this study, we exposed rat hippocampal slices to different convulsants before measuring EAAT activity. Rats were exposed to the EAAT inhibitor pyrrolidine-2,4-dicarboxylic acid (PDC) before entorhinal cortex/hippocampal slices were obtained. These slices were exposed to low-Mg2+ buffer while electrophysiological recordings were obtained from the entorhinal cortex. mGluR III acting agents were used to study whether activation of mGluR III could regulate EAAT activity and if this regulation could overcome the effects on EAAT activity induced by the convulsants.

RESULTS:

Veratridine, kainic acid (KA), and pilocarpine reduced EAAT activity in rat hippocampal slices. L-2-Amino-4-phosphonobutyric acid (an mGluR III agonist) restored EAAT activity and reduced epileptiform activity to near control levels. The saturation curve for glutamate uptake in slices from KA-seized rats killed 2 hours after the first forelimb clonus was displaced to the left, suggesting a compensatory change for the enhanced excitation. On the other hand, rats injected with the EAAT inhibitor PDC (by intracerebroventricular injection) had more severe KA-induced seizures and N-methyl-D-aspartate epileptiform activity than control rats. Furthermore, hippocampal slices from KA- or KA+PDC-treated rats exposed to low Mg2+ reduced their firing rate to nearly zero once they returned to normal solution, whereas their control counterparts continued to fire, although at a lower rate.

CONCLUSIONS:

These results suggest a significant contribution of EAATs in some experimental epilepsy models and point to their short-term regulation by mGluR III as a possible source of their plasticity.

• Authors: O I Claudio, P Ferchmin, L Velísek, E F Sperber, S L Moshé, J G Ortiz
• Journal: Epilepsia (Epilepsia) Vol. 41 Suppl 6 Pg. S104-10 ( 2000) ISSN: 0013-9580 [Print] United States
• PMID: 10999530 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-amino-4-phosphono-propinate
• Dicarboxylic Acids
• Neurotransmitter Uptake Inhibitors
• Propionates
• Pyrrolidines
• Receptors, Glutamate
• Receptors, Metabotropic Glutamate
• metabotropic glutamate receptor 3
• Pilocarpine
• Glutamic Acid
• Veratridine
• pyrrolidine-2,4-dicarboxylic acid
• Magnesium
• Kainic Acid

Topics

• Animals
• Dicarboxylic Acids (pharmacology)
• Epilepsy (physiopathology)
• Female
• Glutamic Acid (metabolism)
• Hippocampus (drug effects, metabolism, physiopathology)
• Kainic Acid (pharmacology)
• Magnesium (pharmacology)
• Neuronal Plasticity
• Neurotransmitter Uptake Inhibitors (pharmacology)
• Pilocarpine (pharmacology)
• Propionates (pharmacology)
• Pyrrolidines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Glutamate (drug effects, physiology)
• Receptors, Metabotropic Glutamate (drug effects)
• Up-Regulation (physiology)
• Veratridine (pharmacology)