Characterization of Mutant Human Brain Sodium Channels Associated with Familial Epilepsy

Abstract

Investigating genetic forms of epilepsy allows for improved understanding of epilepsy pathophysiology in general. Mutations in voltage-gated sodium channels are a frequent cause of genetic forms of epilepsy. First we constructed a computational model of one sodium channel isoform and an epilepsy-associated mutation that refined our knowledge of how sodium channels inactivate. We next utilized a heterologous expression system to biophysically and biochemically characterize epilepsy-associated mutations. We found that aberrant cell surface expression as well as biophysical abnormalities may underlie some epilepsy syndromes. Finally we performed experiments in a transgenic mouse model system of epilepsy to examine the effect of genetic modifiers on sodium channel function. In summary, this research utilized three different model systems to improve our understanding of genetic forms of epilepsy.