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

Abstract

In cardiac myocytes, the voltage-gated sodium channel NaV1.5 opens in response to membrane depolarisation and initiates the action potential. The NaV1.5 channel is typically associated with regulatory β-subunits that modify gating and trafficking behaviour. These β-subunits contain a single extracellular immunoglobulin (Ig) domain, a single transmembrane α-helix and an intracellular region. Here we focus on the role of the β1 and β3 subunits in regulating NaV1.5. We catalogue β1 and β3 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. (Figure presented.).