Long QT syndrome: cellular basis and arrhythmia mechanism in LQT2

Abstract

LQT2 is one form of the congenital long QT syndrome. It results from mutations in the human ether-a-go-go-related gene (HERG), and more than 80 mutations, usually causing single amino acid substitutions in the HERG protein, are known. HERG encodes the ion channel pore-forming subunit protein for the rapidly activating delayed rectifier K+ channel (I(Kr)) in the heart. This review summarizes current findings about mutations causing LQT2, the mechanisms by which mutations may cause the clinical phenotype of a reduction in I(Kr) and a prolonged QT interval, and how this may be involved in the generation of ventricular arrhythmias.