LQT1-phenotypes in hiPSC: Are we measuring the right thing?

Jervell and Lange-Nielsen syndrome presents with deafness and syncopal attacks. Prolongation of QT-duration was identified as a hallmark of the disease, which became the first “long-QT syndrome” (LQT-syndrome). Genetic studies revealed a mutation in a gene encoding a voltage potassium channel, which was called KVLQT1. When coexpressed with the correct accessory subunit, KVLQT1 was shown to generate a slowly activating component of the delayed rectifier potassium current (IKs) (1, 2). The role of IKs for cardiac action potential (AP) configuration has remained enigmatic for some time. IKs-Blocker did not affect AP configuration in multicellular preparations of dog hearts, despite the fact that both compounds effectively block IKs in …