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Annu Rev Physiol. 2015;77:481-504. doi: 10.1146/annurev-physiol-021014-071846.

Sodium channel β subunits: emerging targets in channelopathies.

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Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan 48109; email:


Voltage-gated sodium channels (VGSCs) are responsible for the initiation and propagation of action potentials in excitable cells. VGSCs in mammalian brain are heterotrimeric complexes of α and β subunits. Although β subunits were originally termed auxiliary, we now know that they are multifunctional signaling molecules that play roles in both excitable and nonexcitable cell types and with or without the pore-forming α subunit present. β subunits function in VGSC and potassium channel modulation, cell adhesion, and gene regulation, with particularly important roles in brain development. Mutations in the genes encoding β subunits are linked to a number of diseases, including epilepsy, sudden death syndromes like SUDEP and SIDS, and cardiac arrhythmia. Although VGSC β subunit-specific drugs have not yet been developed, this protein family is an emerging therapeutic target.


arrhythmia; cell adhesion; development; epilepsy; neurodegenerative disease; pain

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