Voltage-gated sodium channel, tetrodotoxin-sensitive (Nav) (TTX-S Nav)

Voltage-gated sodium channels (Nav) are integral membrane proteins that facilitate the rapid influx of sodium ions into cells, a process fundamental to the generation and propagation of action potentials in neurons and muscle cells (Catterall, 2000). The tetrodotoxin-sensitive (TTX-S) class specifically refers to the isoforms Nav1.1, Nav1.2, Nav1.3, Nav1.4, Nav1.6, and Nav1.7, which are inhibited by nanomolar concentrations of the toxin tetrodotoxin (Goldin, 2001). These channels are primarily expressed in the central and peripheral nervous systems and skeletal muscle, where they regulate excitability and signal transmission (Eijkelkamp et al., 2012). Dysregulation or mutations in TTX-S channels are associated with a variety of neurological and muscular disorders, including epilepsy, chronic pain, and periodic paralysis (Meisler & Kearney, 2005). Consequently, they are major therapeutic targets for local anesthetics, anticonvulsants, and analgesics, which modulate channel activity to treat conditions characterized by hyperexcitability (Bagal et al., 2015).

Other names

TTX-sensitive sodium channelsTetrodotoxin-sensitive voltage-gated sodium channelsNav1.1Nav1.2Nav1.3Nav1.4Nav1.6Nav1.7Sodium channel protein type 1 subunit alphaSodium channel protein type 2 subunit alphaSodium channel protein type 3 subunit alphaSodium channel protein type 4 subunit alphaSodium channel protein type 8 subunit alphaSodium channel protein type 9 subunit alpha

Inhibition of sodium ion influx through the channel pore, often by binding to the local anesthetic receptor site in the S6 segment of the alpha subunit, which stabilizes the channel in its non-conducting inactivated state and reduces cellular excitability (Catterall, 2000; Bagal et al., 2015).