Abstracts

Rationale: The potassium channel subunits KCNQ2 and KCNQ3 mediate the M-current in hippocampal neurons. The M-currents regulate neuronal excitability and are believed to mediate neuronal excitability and various mutations of these channels have been linked to benign familial neonatal seizures (BFNS). KCNQ2/3 expression changes during development has been suggested to contribute to the onset of BFNS. Methods: We have used the pilocarpine rat model of Temporal lobe epilepsy in Wistar Rats to determine expression levels of KCNQ2 and KCNQ3 in the hippocampus. Protein expression for KCNQ2 and KCNQ3 was measured using western blots. Gene expression analysis was performed using using real-time PCR and In Situ Hybridization. Results: We found that KCNQ2 and KCNQ3 expression is significantly downregulated nearly 25% and 20% respectively compared to saline injected controls. This decrease was observed 48 hour after seizure onset (*p<0.05). Gene expression analysis using real-time PCR showed a 20% downregulation of mRNA expression of KCNQ2 and KCNQ3 subunits at ages P14 and P21 (*p<0.05). In Situ hybridization experiments showed a marked downregulation of KCNQ3 gene expression in CA1 pyramidal cell neurons of the hippocampus. Conclusions: There is a significant decrease in KCNQ2 and KCNQ3 expression following seizures, which suggest a role of KCNQ channel expression in epileptogenesis. These results support the putative role of KNCQ2/3 expression changes in the development of BFNS. Supported by NS 046516