Altered Expression of Zonula occludens-1 Affects Cardiac Na⁺ Channels and Increases Susceptibility to Ventricular Arrhythmias.

ABSTRACT: Zonula occludens-1 (ZO-1) is an intracellular scaffolding protein that orchestrates the anchoring of membrane proteins to the cytoskeleton in epithelial and specialized tissue including the heart. There is clear evidence to support the central role of intracellular auxiliary proteins in arrhythmogenesis and previous studies have found altered ZO-1 expression associated with atrioventricular conduction abnormalities. Here, using human cardiac tissues, we identified all three isoforms of ZO-1, canonical (Transcript Variant 1, TV1), CRA_e (Transcript Variant 4, TV4), and an additionally expressed (Transcript Variant 3, TV3) in non-failing myocardium. To investigate the role of ZO-1 on ventricular arrhythmogenesis, we generated a haploinsufficient ZO-1 mouse model (ZO-1

SUBMITTER: El Refaey M 

PROVIDER: S-EPMC8870063 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature