sodiumkanaler

Sodiumkanaler, or voltage-gated sodium channels, are a family of transmembrane proteins that conduct sodium ions across the cell membrane in response to changes in membrane potential. They are essential for the initiation and propagation of action potentials in neurons, skeletal muscle, and many other excitable cells. The core functional unit is the alpha subunit, encoded by several SCN genes, with multiple isoforms named Nav1.1 through Nav1.9. Each alpha subunit contains four homologous domains (I–IV), and each domain has six transmembrane segments (S1–S6). The S5–S6 segments form the ion-conducting pore, while the S1–S4 segments serve as the voltage-sensing domain. An intracellular loop between domains III and IV acts as the fast inactivation gate, rapidly stopping Na+ flow after activation. Auxiliary beta subunits modulate gating, kinetics and localization.

Nav isoforms show distinct tissue distribution. Neuronal isoforms such as Nav1.1–Nav1.3 are prominent in the central nervous system, Nav1.7–Nav1.9 are common in peripheral nerves, Nav1.4 is found in skeletal muscle, and Nav1.5 predominates in cardiac tissue. Upon depolarization, channels open quickly to produce the fast sodium current (INa) that drives the rising phase of the action potential; inactivation follows to terminate the current, enabling repolarization. Gating is influenced by voltage, phosphorylation, lipids, and protein interactions.

Pharmacology and clinical relevance: many sodiumkanaler are sensitive to tetrodotoxin, though Nav1.5, Nav1.8, and Nav1.9 show relative resistance. Local anesthetics and certain antiarrhythmic drugs block the inner pore to inhibit channel activity. Mutations in SCN genes can cause channelopathies, including epilepsy (e.g., SCN1A), pain disorders (e.g., SCN9A), periodic paralysis (SCN4A), and cardiac arrhythmias (SCN5A).