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

Published version
Peer-reviewed

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Type

Article

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Authors

Salvage, Samantha C  ORCID logo  https://orcid.org/0000-0002-5793-2349
Huang, Christopher L-H 

Abstract

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 trans-cell-adhesion between β1-associated Nav1.5 subunits on the intercalated disc and promote ephaptic conduction between cardiomyocytes.

Description

Keywords

voltage-gated sodium (Nav) channels, Nav1.5, sodium (Nav) channel β-subunits, cell-adhesion, ephaptic conduction

Journal Title

Biomolecules

Conference Name

Journal ISSN

2218-273X

Volume Title

10

Publisher

MDPI
Sponsorship
British Heart Foundation (PG/14/79/31102, PG/19/59/34582)
Isaac Newton Trust (G101770)