Abstracts

Kainate (KA) receptors are formed from homomeric or heteromeric combinations of subunits, including GluR5 and GluR6. Studies with transgenic mice indicate that KA receptors containing GluR6 subunits play a role in KA-induced seizures (1). Here we used kainate receptor knockout (KO) mice to determine the clinical seizure and EEG correlates of GluR5 kainate receptor activation, and the roles of kainate receptor subunits in other seizure models., Video-EEG monitoring was carried out during slow tail vein infusion of the selective GluR5 agonist ATPA in wild type (WT), GluR5-/-, and GluR6-/- mice. We also assessed seizure thresholds using the i.v. PTZ and 6 Hz models., Slight myoclonic jerks/twitches associated with single sharp waves occurred at lower doses of ATPA in WT than in GluR5-/-, but generalized seizures occurred at similar doses. Myoclonic jerks occurred at comparable doses in WT and GluR6-/- mice; paradoxically, EEG seizure patterns began with lower doses in GluR6-/- mice. There were no significant differences between any of the genotypes in their thresholds for clonic seizures induced by i.v. PTZ or in the 6 Hz seizure model., GluR5 kainate receptors contribute to ATPA-induced myoclonic jerks, but not to generalized seizures. The increased sensitivity of GluR6 KO mice to ATPA was unexpected. In the KO animals, the existence of GluR5 homomers instead of GluR5/GluR6 heteromers may account for the phenomenon since GluR5 homomers are about 2.4-fold more sensitive to ATPA than are GluR5/GluR6 heteromers (2). GluR5 and GluR6 kainate receptors do not appear to play a role in seizure activity in the PTZ and 6 Hz models.
(1) Mulle C, Sailer A, Perez-Otano I, et al. Nature 1998;392:601-605.
(2) A. Alt , B. Weiss, A.M. Ogden, et al. Neuropharmacology 2004; 46:793-806.,