Abstracts

RATIONALE: Epilepsy in children is frequently associated with cortical dysplasia (CD). CD is characterized by anatomical malformations and the presence of cytomegalic neurons. It has been suggested that these neurons display altered sensitivity to excitatory and inhibitory amino acids. The present study examined the responsiveness of acutely dissociated neurons from slices of tissue resected for the treatment of catastrophic pediatric epilepsy. METHODS: Cells were obtained from five cases (9 weeks to 5.6 years). Neurons were acutely isolated using enzymatic digestion with papain (1 mg/ml, 30-40 minutes), followed by mechanical dissociation. Voltage clamp recordings were made using micropipettes (2.5-3.5 M?) containing N-methyl-D-glucamine based internal solution. We analyzed NMDA and GABA current densities, NMDA dose response, and sensitivity to magnesium. Where possible, comparisons were made between cells from least and most epileptogenic samples. RESULTS: All neurons (N=26) responded to application of N-methyl-D-aspartate (NMDA, .01 to 1 mM) and GABA (100 M). No clear differences in GABA or NMDA responsiveness were observed. In one case (9 weeks old) cytomegalic neurons from the most epileptogenic sample were observed and recorded. These cells (N=4) also responded to NMDA and GABA, but displayed reduced sensitivity to magnesium blockade. CONCLUSIONS: Acutely dissociated neurons from dysplastic cortex respond to both NMDA and GABA. No obvious changes in responsiveness to these amino acids were found between cells from least and most epileptogenic samples. However, cytomegalic neurons appear to have altered sensitivity to magnesium. This suggests that cytomegalic neurons could exhibit differential NMDA receptor subunit composition. Supported by: USPHS NS 28383, 38992 and 36536