Sodium channel protein type 1 subunit alpha (Nav1.1) (Nav1.1)

Sodium channel protein type 1 subunit alpha (Nav1.1) is a voltage-gated sodium channel primarily expressed in the central nervous system, particularly in the axon initial segments of inhibitory GABAergic interneurons [5, 6]. It plays a critical role in maintaining the excitability and high-frequency firing of these interneurons, which are essential for balancing excitation and inhibition in the brain [25, 30]. Mutations in the SCN1A gene, which encodes Nav1.1, are the most common cause of genetic epilepsies, including Dravet syndrome and Generalized Epilepsy with Febrile Seizures plus (GEFS+) [25, 26]. Therapeutic strategies often focus on activating Nav1.1 to restore inhibitory tone or avoiding its inhibition to prevent seizure exacerbation [4, 26]. Drug development for this target requires high selectivity over other sodium channel isoforms, such as Nav1.6 (to avoid over-exciting excitatory neurons) and Nav1.4/Nav1.5 (to avoid skeletal muscle and cardiac side effects) [4, 31]. Selective Nav1.1 activators, such as the peptide Hm1a and small molecule AA43279, are being investigated as precision medicines to treat Dravet syndrome by specifically enhancing the function of the remaining wild-type channels [23, 26, 41].

Other names

SCN1ASodium channel protein brain I subunit alphaVoltage-gated sodium channel subunit alpha Nav1.1NAC1FEB3FEB3AGEFSP2HBSCISMEINeural-biased sodium channel

Positive allosteric modulation (activation) or inhibition (pore blocking and gating modification)