Abstracts

RATIONALE: Activation of group I metabotropic glutamate receptors (mGluR) initiates a cascade of second messengers that results in seizures in vivo and epileptiform activity in vitro. The in vitro epileptiform activity includes brief interictal discharges (< 500 ms) and prolonged (> 2 s) discharges composed of 4-20 Hz activity that resemble ictal epileptiform discharges. We investigated the dependence of ictal discharges on activation of NMDA receptors or voltage dependent calcium channels. METHODS: Hippocampal slices were prepared from adult rats and maintained in an interface chamber. After a 1 h. incubation, slices were exposed to 100 ?M R,S-3-5 dihyroxyphenylglycine (DHPG, a specific group I mGluR agonist) for 2 hours. Extracellular recordings were made from the CA3 region. The activity was characterized as ictal (> 2 s long at > 2 Hz) or interictal. The duration of ictal discharges and the time between ictal discharges were measured before and after NMDA and calcium channel antagonists. RESULTS: DL-2-amino-5-phosphonopentanoic acid (APV, 100?M) did not significantly change the pattern of activity produced by DHPG. Ictal discharges stopped in 1 of 7 slices. In the other 6 slices, ictal activity continued (discharge duration 5.5 ? 0.4 s before and 6.5 ? 0.8 s after APV; interval between discharges 37 ? 7 s in control and 35 ? 7 s in APV). The high threshold calcium channel blocker nifedipine (1 ?M) converted ictal patterns to interictal discharges in 12 of 14 slices. Nickel ( Ni++ 50 ?M) which blocks low threshold calcium channels, did not alter the duration of ictal discharges (5.7 ? 0.6 s in control vs. 6.1 ? 0.8 s in Ni++ ) or the time between their occurence (43 ? 13 vs. 40 ? 12 s). CONCLUSIONS: Prolonged epileptiform discharges produced by activation of group I mGluR were not dependent on NMDA receptor activation. Blockade of high threshold L-type calcium channels suppressed ictal discharges, and low threshold calcium channel blockade did not influence ictal patterns. These findings support a role for L-type calcium channel activation in the expression of synchronous epileptiform oscillations produced by group I mGluRs. Supported by VA research