Long QT syndrome: Ionic basis and arrhythmia mechanism in long QT syndrome type 1

Long QT syndrome type 1 (LQT1) causes torsades de pointes arrhythmia, ventricular fibrillation, and sudden death. It usually is inherited as an autosomal dominant trait (Romano-Ward syndrome). The primary defect in LQT1 is a mutation in KVLQTY1, a gene that encodes the pore-forming alpha-subunit of K+ channel. KvLQT1 alpha-subunits coassemble with minK beta-subunits to form channels that conduct the slow delayed rectifier K+ current (I-Ks) in the heart. Recessive mutations in KVLQT1 cause Jervell and Lange-Nielsen syndrome, which is characterized by more severe arrhythmias and congenital neural deafness. Heterologous expression studies demonstrated that mutations in KVLQT1 reduce I-Ks by causing loss of channel function, altered channel gating. and/or a dominant-negative effect. It remains to be proven that an understanding of the molecular basis of LQT1 will lead to more effective therapy.