Abstracts

Rationale: During induction of kindled seizures with pentylenetetrazol (PTZ) we found rats developed stage 5 seizures at different rates. We wondered whether there are differences in kindling progression that might be related to the molecular regulation of glutamate transporters. Methods: Rats were kindled with PTZ; we collected animals that were resistant to kindling, having failed to achieve the fully kindled state even after 12 consecutive injections of PTZ. We removed hippocampal structures and measured the glutamate transporters GLAST, GLT-1 and EAAC1. Glutamine synthetase (GS) and small neuronal acid transporter (sNAT2) were measured; real-time PCR was used to measure mRNA expression. Results: We found significant increases in the levels of the glutamate transporters GLAST, GLT-1, EAAC1, GS and sNAT2 mRNA in kindling resistant rats when compared to those easily kindled. Conclusions: Glutamate is taken up by glial cells via GLAST and GLT-1 and then converted to glutamine by GS. Glutamine is transported into neurons by sNAT1 or 2. Up-regulation of genes involved in glutamate transport in kindling resistant animals supports the hypothesis that clearance of glutamate from extracellular space and conversion to glutamine within glia attenuates kindling.