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Review
. 2015:77:481-504.
doi: 10.1146/annurev-physiol-021014-071846.

Sodium channel β subunits: emerging targets in channelopathies

Heather A O'Malley  1 , Lori L Isom
Affiliations
Review

Sodium channel β subunits: emerging targets in channelopathies

Heather A O'Malley et al. Annu Rev Physiol. 2015.

Abstract

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.

Keywords: arrhythmia; cell adhesion; development; epilepsy; neurodegenerative disease; pain.

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Figures

Figure 1
Figure 1
Disease-linked mutations in VGSC β subunits. Sites of mutated amino acids for each of the five β subunit protein products are denoted, including epilepsy (yellow), cardiac disease and non-SUDEP sudden death (red), cancer (blue), and mutations which have been identified in patients with multiple diagnoses (white). In β1/β1B, epilepsy-linked mutations cluster around the Ig loop, while no mutations have so far been identified in the Ig loop of β2 or β4, but instead occur within the transmembrane domain and C-terminus. Mutations in β3 occur throughout the protein.
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