Revealing the Concealed Nature of Long-QT Type 3 Syndrome.

ABSTRACT:

Background

Gain-of-function mutations in the voltage-gated sodium channel (Nav1.5) are associated with the long-QT-3 (LQT3) syndrome. Nav1.5 is densely expressed at the intercalated disk, and narrow intercellular separation can modulate cell-to-cell coupling via extracellular electric fields and depletion of local sodium ion nanodomains. Models predict that significantly decreasing intercellular cleft widths slows conduction because of reduced sodium current driving force, termed "self-attenuation." We tested the novel hypothesis that self-attenuation can "mask" the LQT3 phenotype by reducing the driving force and late sodium current that produces early afterdepolarizations (EADs).

Methods and results

Acute interstitial edema was used to increase intercellular cleft width in

SUBMITTER: Greer-Short A 

PROVIDER: S-EPMC5319726 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature