Kcne4 deletion sex-specifically predisposes to cardiac arrhythmia via testosterone-dependent impairment of RISK/SAFE pathway induction in aged mice.

ABSTRACT: Sudden cardiac death (SCD) is associated with both electrical and ischemic substrates, and is a major cause of ischemic heart disease mortality worldwide. Male sex predisposes to SCD but the underlying mechanisms are incompletely understood. KCNE4, a cardiac arrhythmia-associated potassium channel β-subunit, is upregulated by 5α-dihydrotestosterone (DHT). Thus, ventricular Kcne4 expression is low in young adult female mice, but high in males and postmenopausal (12+ months) females. Despite causing a sex-independent electrical substrate at 13 months of age (22% QT prolongation in both males and females; P < 0.01), Kcne4 deletion preferentially predisposed aged male mice to ischemia/reperfusion (IR)-provoked ventricular tachyarrhythmias. Interestingly, Kcne4 deletion caused baseline inductio

SUBMITTER: Hu Z 

PROVIDER: S-EPMC5974354 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature