A Possible Explanation for the Low Penetrance of Pathogenic KCNE1 Variants in Long QT Syndrome Type 5.

ABSTRACT: Long QT syndrome (LQTS) is an inherited cardiac rhythm disorder associated with increased incidence of cardiac arrhythmias and sudden death. LQTS type 5 (LQT5) is caused by dominant mutant variants of KCNE1, a regulatory subunit of the voltage-gated ion channels generating the cardiac potassium current I_Ks. While mutant LQT5 KCNE1 variants are known to inhibit I_Ks amplitudes in heterologous expression systems, cardiomyocytes from a transgenic rabbit LQT5 model displayed unchanged I_Ks amplitudes, pointing towards the critical role of additional factors in the development of the LQT5 phenotype in vivo. In this study, we demonstrate that KCNE3, a candidate regulatory subunit of I_Ks channels minimizes the inhibitory effects of LQT5 KCNE1 variants on

SUBMITTER: Deri S 

PROVIDER: S-EPMC9782992 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature