Cardiac sodium channel complexes and arrhythmia: structural and functional roles of the β1 and β3 subunits

In cardiac myocytes, the voltage-gated sodium channel Na(V)1.5 opens in response to membrane depolarisation and initiates the action potential. The Na(V)1.5 channel is typically associated with regulatory beta-subunits that modify gating and trafficking behaviour. These beta-subunits contain a single extracellular immunoglobulin (Ig) domain, a single transmembrane alpha-helix and an intracellular region. Here we focus on the role of the beta 1 and beta 3 subunits in regulating Na(V)1.5. We catalogue beta 1 and beta 3 domain specific mutations that have been associated with inherited cardiac arrhythmia, including Brugada syndrome, long QT syndrome, atrial fibrillation and sudden death. We discuss how new structural insights into these proteins raises new questions about physiological function.

Automated summary

The paragraph discusses the role of the beta 1 and beta 3 subunits in regulating the Na(V)1.5 sodium channel in cardiac myocytes, and how specific mutations in these subunits are associated with inherited cardiac arrhythmias. It also highlights new structural insights that raise questions about the physiological function of these proteins.