Regulation of potassium channel genes important in epilepsy.

Epilepsy is the second most common neurological disorder affecting 1 in 130 people in the UK. Every day 100 new patients are diagnosed as epileptic and 1 in 20 people will suffer a seizure at some point in their lives. Epileptic seizures are the result of episodes of abnormally high neuronal activity which can be induced by one of many factors. Two genes that are mutated in a form of epilepsy, KCNQ2 and KCNQ3, encode subunits of a potassium channel (K v 7) that regulates the resting membrane potential of neurones and controls excitability. Despite their importance in disease almost nothing is known about how the expression of these genes is controlled in normal or epileptic nervous systems. Once a seizure has occurred an individual becomes more susceptible to further seizures. Although it is known that this effect requires changes in gene expression, the exact nature of those changes is not understood. It is likely that changes in expression of genes that regulate neuronal excitability would be important for this response to seizure activity. To investigate how such genes are regulated we have isolated the genes, KCNQ2 and KCNQ3, and have used bioinformatic analysis, DNase I sensitivity, gel retardation assays and reporter gene assays to identify functional promoter elements within these genes. We show that KCNQ2 and KCNQ3 are regulated by at least some shared transcription factors that respond to seizure activity and that expression levels of these genes in cultured neurones are responsive to neuronal activity.