Epilepsy is the second most common neurological disease and 1 in 20 individuals will suffer an epileptic event sometime during their lifetime. 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, which encode two potassium channel subunits of the M-channel and function to regulate neuronal excitability. Mutations in either KCNQ2 or KCNQ3, resulting in diminished function in humans are responsible for a form of epilepsy indicating the important role of these subunits. We have used bioinformatic analysis, DNase I sensitivity, gel retardation assays and reporter gene assays to identify functional promoter elements within the human KCNQ2 gene. 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 neurons are responsive to neuronal activity.