Temperature sensitivity of febrile seizure sodium channel mutations

Altered temperature sensitivity of familial sodium channel mutations in epilepsy as a unifying mechanism for genesis of febrile seizures

Generalised Epilepsy with Febrile Seizures Plus (GEFS+) type 1 is characterised by a C121W point mutation in the ?1 subunit of the voltage gated sodium channel. People afflicted with this condition display seizures initiated by fever up until six years of age, and then display febrile or afebrile seizures into adulthood. Previous published studies using cell lines have shown that this sodium channel mutation alters the functionality of the channel. The aim of this project is to study the sodium channel's kinetics properties with changes in temperature that correspond to both normal and fever body temperatures in humans. Data so far show changes in channel kinetics as well as differing temperature sensitivities of the mutated channel compared to the normal channel. Preliminary data at fever temperature indicate that changes in temperature sensitivity may cause a higher susceptibility to seizures. Future work will entail action potential firing property studies of neurons in C121W mouse models as well as investigating a new technique called Dynamic Clamping that may enable action potential firing properties of mutated ion channels to be understood in simple cultured cells such as human embryonic kidney (HEK293) cells instead of neurons.