Voltage-gated sodium channel β-subunits may act as cell-adhesion molecules interacting uniquely with Nav1.5 to facilitate trans-cell-adhesion and promote ephaptic conduction between cardiomyocytes.
This review highlights the role of Nav channel β-subunits as cell-adhesion molecules that may uniquely interact with Nav1.5 to facilitate ephaptic conduction in the heart.
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.
Salvage et al. (Wed,) reported a review. Voltage-gated sodium channel β-subunits may act as cell-adhesion molecules interacting uniquely with Nav1.5 to facilitate trans-cell-adhesion and promote ephaptic conduction between cardiomyocytes.
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