Nav1.1 exists in three distinct states: deactivated (closed), activated (open), or inactivated (closed). Nav1.1 is tetrodotoxin (TTX) sensitive with similar kinetics. The gating properties control action potential initiation and repetitive firing in neurons. The β subunits may modify the kinetics and voltage dependence of gating.

Although expressed widely in the CNS, Nav1.1 expresses more predominantly in the inhibitory interneuron, shown in SCN1A-knockout mice that the sodium current density was reduced in the inhibitory interneurons, but not in the excitatory pyramidal neurons. This explains why loss of function in Nav1.1 can lead to hyperexcitability of brain and cause epilepsy.

Our previous study has demonstrated that the patients with partial epilepsy and FS+ were associated with loss of function of Nav1.1 and seizure aggravations by sodium-blocking antiepileptic drugs (AEDs), suggesting a potential link between functional alteration and response to AEDs (DOI 10.1111/j.1528-1167.2010.02645.x). Defining functional alteration of Nav1.1 mutants is therefore potentially significant in optimizing treatment for individual patient.