Cell-Adhesion Properties of ß-Subunits in the Regulation of Cardiomyocyte Sodium Channels.
Biomolecules
; 10(7)2020 07 01.
Article
in En
| MEDLINE
| ID: mdl-32630316
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 ß-subunits (ß1-4) bind to the Nav channel α-subunits. Previous work has emphasised the ß-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 ß-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 ß-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 ß1-associated Nav1.5 subunits on the intercalated disc and promote ephaptic conduction between cardiomyocytes.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Myocytes, Cardiac
/
NAV1.5 Voltage-Gated Sodium Channel
/
Voltage-Gated Sodium Channel beta Subunits
Limits:
Animals
/
Humans
Language:
En
Journal:
Biomolecules
Year:
2020
Document type:
Article
Affiliation country:
United kingdom