Sodium channel β subunits: emerging targets in channelopathies

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


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.

Publication types

  • Review

MeSH terms

  • Arrhythmias, Cardiac / genetics
  • Arrhythmias, Cardiac / physiopathology
  • Autistic Disorder / genetics
  • Autistic Disorder / physiopathology
  • Cell Adhesion / genetics
  • Cell Adhesion / physiology
  • Channelopathies / genetics*
  • Channelopathies / physiopathology*
  • Epilepsy / genetics
  • Epilepsy / physiopathology
  • Gene Expression Profiling
  • Humans
  • Mutation / genetics*
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / physiopathology
  • Protein Processing, Post-Translational / genetics
  • Protein Processing, Post-Translational / physiology
  • Voltage-Gated Sodium Channel beta Subunits / genetics*
  • Voltage-Gated Sodium Channel beta Subunits / physiology*


  • Voltage-Gated Sodium Channel beta Subunits