Sodium channel protein type 3 subunit alpha (NaV1.3) (NaV1.3)

Voltage-gated sodium channel NaV1.3, encoded by the SCN3A gene, is a transmembrane protein essential for the generation and propagation of action potentials in excitable cells [2, 5]. It is predominantly expressed in the central nervous system during fetal development, with levels significantly declining in the adult brain under normal conditions [5, 6]. However, NaV1.3 can be re-expressed or upregulated in adult neurons following nerve injury, traumatic brain injury, or during chronic seizures, contributing to neuronal hyperexcitability and maladaptive neural responses [1, 9]. This channel is a critical therapeutic target for the treatment of neuropathic pain and various forms of epilepsy, including drug-resistant cases associated with SCN3A mutations [5, 7]. Pharmacological modulation of NaV1.3 involves the use of sodium channel blockers like bulleyaconitine A and tricyclic antidepressants, which stabilize the channel in a non-conductive state to dampen abnormal firing [1, 2, 5]. Despite its therapeutic potential, developing selective NaV1.3 inhibitors remains challenging due to the high structural similarity among sodium channel subtypes, which can lead to off-target effects in the central nervous and cardiovascular systems [2, 11].

Other names

SCN3ASodium channel protein type III alpha subunitNAC3Voltage-gated sodium channel type III alphaNav1.3

Sodium channel blocker that stabilizes the channel in a non-conductive state, inhibiting the flow of sodium ions and reducing neuronal excitability.