Function

Na_v1.1 exists in three distinct states: deactivated (closed), activated (open), or inactivated (closed). Na_v1.1 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, Na_v1.1 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 Na_v1.1 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 Na_v1.1 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 Na_v1.1 mutants is therefore potentially significant in optimizing treatment for individual patient.