Voltage-gated sodium channel protein (local anesthetic site)

Voltage-gated sodium channels (Navs) are large transmembrane proteins essential for the initiation and propagation of action potentials in excitable cells such as neurons, muscle fibers, and cardiac tissue. They are the primary molecular targets for local anesthetic drugs, which block nerve conduction by inhibiting sodium influx through these channels. The core functional unit is the α-subunit, a single polypeptide with four homologous domains (I–IV), each containing six transmembrane segments (S1–S6). The S4 segment in each domain acts as a voltage sensor. The pore-forming region consists of P-loops between S5 and S6 segments from all four domains; this region determines ion selectivity. Accessory β-subunits modulate channel gating and localization. Local anesthetics bind within the inner pore of the channel, primarily interacting with residues on S6 segments—especially a conserved phenylalanine in domain IV S6. Drug binding is state-dependent: affinity increases when channels are open or inactivated. Local anesthetics inhibit sodium current by physically blocking ion permeation through steric occlusion at their binding site within the inner pore and modulating gating by stabilizing certain conformational states.

Other names

Nav channelSodium channelVoltage-gated Na+ channelVGSC

Blockade/modulation via inner pore binding—state-, voltage-, use-dependent