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Article
Role of GluK1 Kainate Receptors in Seizures, Epileptic Discharges, and Epileptogenesis
Journal of Neuroscience (2014)
  • Brita Fritsch
  • Janine Reis
  • Maciej Gasior, Drexel University
  • Rafal M. Kaminski
  • Michael A. Rogawski, University of California - Davis
Abstract
Kainate receptors containing the GluK1 subunit have an impact on excitatory and inhibitory neurotransmission in brain regions, such as the amygdala and hippocampus, which are relevant to seizures and epilepsy. Here we used 2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), a potent and selective agonist of kainate receptors that include the GluK1 subunit, in conjunction with mice deficient in GluK1 and GluK2 kainate receptor subunits to assess the role of GluK1 kainate receptors in provoking seizures and in kindling epileptogenesis. We found that systemic ATPA, acting specifically via GluK1 kainate receptors, causes locomotor arrest and forelimb extension (a unique behavioral characteristic of GluK1 activation) and induces myoclonic behavioral seizures and electrographic seizure discharges in the BLA and hippocampus. In contrast, the proconvulsant activity of systemic AMPA, kainate, and pentylenetetrazol is not mediated by GluK1 kainate receptors, and deletion of these receptors does not elevate the threshold for seizures in the 6-Hz model. ATPA also specifically activates epileptiform discharges in BLA slices in vitro via GluK1 kainate receptors. Olfactory bulb kindling developed similarly in wild-type, GluK1, and GluK2 knock-out mice, demonstrating that GluK1 kainate receptors are not required for epileptogenesis or seizure expression in this model. We conclude that selective activation of kainate receptors containing the GluK1 subunit can trigger seizures, but these receptors are not necessary for seizure generation in models commonly used to identify therapeutic agents for the treatment of epilepsy.
Keywords
  • ATPA,
  • BLA,
  • epilepsy,
  • kainate receptor,
  • kindling,
  • seizure
Publication Date
April 23, 2014
Publisher Statement
Available at: http://dx.doi.org/10.1523/JNEUROSCI.5307-13.2014
This paper was the Featured Article in the Neurobiology of Disease section of the Journal of Neuroscience March 23, 2014 issue. The editor's summary is available here.
Citation Information
Brita Fritsch, Janine Reis, Maciej Gasior, Rafal M. Kaminski, et al.. "Role of GluK1 Kainate Receptors in Seizures, Epileptic Discharges, and Epileptogenesis" Journal of Neuroscience Vol. 34 Iss. 17 (2014)
Available at: http://works.bepress.com/michael_rogawski/64/