sodiumchannel

A sodium channel is a membrane protein pore that selectively conducts Na+ ions and is essential for initiation and propagation of action potentials in neurons and muscle. In vertebrates, these channels are primarily voltage-gated, opening with depolarization and contributing to the rapid upstroke of the action potential.

Molecular architecture features a single alpha subunit (~200–260 kDa) forming the ion-conducting pore, organized into four homologous domains (I–IV) with six transmembrane segments each (S1–S6). The S4 segments are voltage sensors; the S5–S6 region forms the pore. Vertebrates also express auxiliary beta subunits that modulate gating and trafficking. Bacterial sodium channels (e.g., NaChBac) have a simpler single-subunit architecture retaining the core four-domain core.

Gating: depolarization opens the channel (activate), allowing Na+ influx and rapid depolarization. Fast inactivation, mediated by an intracellular linker, terminates the current and shapes the action potential; recovery from inactivation enables repetitive firing.

Genetics and diversity: multiple alpha-subunit genes (SCN1A–SCN11A in humans) encode tissue-specific isoforms; beta subunits (SCN1B–SCN4B) influence expression and kinetics. Channels distribute in central and peripheral neurons, heart, and skeletal muscle.

Pharmacology and disease: local anesthetics and antiarrhythmics block the inner pore or alter gating. Tetrodotoxin blocks many channels, while Nav1.5, Nav1.8, and Nav1.9 are tetrodotoxin-insensitive. Mutations cause channelopathies such as epilepsy, cardiac arrhythmias, periodic paralysis, and migraine; research uses structural biology and heterologous expression to study function and pharmacology.