Cell-Adhesion Properties of β-Subunits in the Regulation of Cardiomyocyte Sodium Channels

• Main Authors: Samantha C Salvage, Christopher L-H Huang, Antony P Jackson
• Format: Article
• Language: English
• Published: MDPI AG 2020-07-01
• Series: Biomolecules
• Subjects: voltage-gated sodium (Nav) channels; Nav1.5; sodium (Nav) channel β-subunits; cell-adhesion; ephaptic conduction
• Online Access: https://www.mdpi.com/2218-273X/10/7/989

Voltage-gated sodium (Nav) channels drive the rising phase of the action potential, essential for electrical signalling in nerves and muscles. The Nav channel α-subunit contains the ion-selective pore. In the cardiomyocyte, Nav1.5 is the main Nav channel α-subunit isoform, with a smaller expression of neuronal Nav channels. Four distinct regulatory β-subunits (β1–4) bind to the Nav channel α-subunits. Previous work has emphasised the β-subunits as direct Nav channel gating modulators. However, there is now increasing appreciation of additional roles played by these subunits. In this review, we focus on β-subunits as homophilic and heterophilic cell-adhesion molecules and the implications for cardiomyocyte function. Based on recent cryogenic electron microscopy (cryo-EM) data, we suggest that the β-subunits interact with Nav1.5 in a different way from their binding to other Nav channel isoforms. We believe this feature may facilitate <i>trans</i>-cell-adhesion between β1-associated Nav1.5 subunits on the intercalated disc and promote ephaptic conduction between cardiomyocytes.