Selective Antagonism of GluR5 Kainate-Receptor-Mediated Synaptic Currents by Topiramate in Rat Basolateral Amygdala Neurons
| Autor: | Michael A. Rogawski, Divina Gryder |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
Topiramate
Male Patch-Clamp Techniques Kainate receptor AMPA receptor Fructose Pharmacology In Vitro Techniques Amygdala Synaptic Transmission Rats Sprague-Dawley Receptors Kainic Acid medicine GRIK1 Animals Neurons biology Chemistry General Neuroscience Electric Stimulation Rats medicine.anatomical_structure Mechanism of action Excitatory postsynaptic potential biology.protein Anticonvulsants medicine.symptom Brief Communications Neuroscience Excitatory Amino Acid Antagonists medicine.drug Basolateral amygdala |
| Popis: | Topiramate is a widely used antiepileptic agent whose mechanism of action is poorly understood. The drug has been reported to interact with various ion channel types, including AMPA/kainate receptors. In whole-cell voltage-clamp recordings from principal neurons of the rat basolateral amygdala, topiramate at low concentrations (IC50, approximately 0.5 microm) selectively inhibited pharmacologically isolated excitatory synaptic currents mediated by kainate receptors containing the GluR5 subunit. Topiramate also partially depressed predominantly AMPA-receptor-mediated EPSCs, but with lower efficacy. Topiramate did not alter the degree of facilitation in paired-pulse experiments, and it reduced the amplitude of miniature EPSCs without affecting their frequency, demonstrating that the block of synaptic responses occurs postsynaptically. Inhibition of GluR5 kainate receptors could represent a key mechanism underlying the anticonvulsant activity of topiramate. Moreover, these results support the concept that GluR5 kainate receptors represent a novel target for antiepileptic drug development. |
| Databáze: | OpenAIRE |
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