Voltage-gated Sodium Channel Blockers

Voltage-gated sodium channels (Na_V) are responsible for action potential initiation and propagation in excitable cells, including nerve, muscle, and neuroendocrine cell types. They are also expressed at low levels in non-excitable cells, where their physiological role is unclear.

Structurally, Na_V channels are composed of one pore-forming α-subunit, which may be associated with either one or more β-subunits. α-subunits are composed of four homologous domains, each of which contains six transmembrane segments. The fourth transmembrane loop (S4) acts as the 'voltage sensor' and is activated by changes in membrane potential. S4 is also involved in channel gating.