Voltage-Gated Sodium Channel Protein (Neuronal) (VGSC (Neuronal))

Voltage-gated sodium channels (VGSCs) are essential transmembrane proteins that enable the rapid influx of sodium ions (Na⁺) into excitable neuronal cells in response to changes in membrane potential. This process is fundamental for the initiation and propagation of action potentials, which underlie neuronal communication. The core functional unit is a large alpha (α) subunit, which forms the ion-conducting pore. The α subunit consists of four homologous domains (I–IV), each containing six transmembrane segments (S1–S6). The S4 segment in each domain acts as a voltage sensor. The region between S5 and S6 within each domain forms the selectivity filter. A cytoplasmic linker between domains III and IV serves as an inactivation gate. Accessory beta (β) subunits modulate channel kinetics and localization. VGSCs cycle through resting, activated/open, and inactivated states. These channels are critical for initiating action potentials, propagating electrical signals, and resetting membrane potential. They are highly expressed at nodes of Ranvier in myelinated axons. VGSCs are major drug targets for local anesthetics, antiepileptics, and antiarrhythmics. Mutations or dysfunction can cause neurological diseases. Multiple genes encode different VGSC isoforms with tissue-specific expression patterns, including Nav1.1–Nav1.9 in neurons.

Other names

Neuronal Sodium ChannelVoltage-Sensitive Sodium Channel (Neuronal)NaV (Neuronal)

Channel blockade; modulation of channel kinetics (activation, inactivation)