Increased L-type calcium current causes action potential prolongation in Jervell and Lange-Nielsen syndrome and is a drug target.

ABSTRACT:

Background

KCNQ1 loss of function variants are thought to cause type 1 long QT syndrome by reducing I _Ks. However, we have recently reported that pharmacologic block of I _Ks in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) produced minimal increases in action potential duration at 90% repolarization (APD₉₀), while genetic loss of KCNQ1 markedly prolonged APD₉₀. We sought here to define mechanisms underlying APD prolongation by genetic loss of KCNQ1.

Methods

We studied iPSC-CMs from population controls, an isogenic KCNQ1 knock out (KO) line created by a homozygous edit for the R518X loss of function variant, and 2 unrelated patients with the Jervell and Lange-Nielsen

SUBMITTER: Wada Y 

PROVIDER: S-EPMC11957160 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature