LQT1 mutations in KCNQ1 C-terminus assembly domain suppress I-Ks using different mechanisms

摘要

Aims Long QT syndrome 1 (LQT1) mutations in KCNQ1 that decrease cardiac I-Ks (slowly activating delayed rectifier K+ current) underlie ventricular arrhythmias and sudden death. LQT1 mutations may suppress I-Ks by preventing KCNQ1 assembly, disrupting surface trafficking, or inhibiting gating. We investigated mechanisms underlying how three LQT1 mutations in KCNQ1 C-terminus assembly domain (R555H/G589D/L619M) decrease I-Ks in heterologous cells and cardiomyocytes.