Modelling the effects of chloroquine on KCNJ2-linked short QT syndrome.

ABSTRACT: A gain-of-function KCNJ2 D172N mutation in KCNJ2-encoded Kir2.1 channels underlies one form of short QT syndrome (SQT3), which is associated with increased susceptibility to arrhythmias and sudden death. Anti-malarial drug chloroquine was reported as an effective inhibitor of Kir2.1 channels. Using biophysically-detailed human ventricle computer models, this study assessed the effects of chloroquine on SQT3. The ten Tusscher et al. model of human ventricular cell action potential was modified to recapitulate functional changes in the inward rectifier K⁺ current (I_K1) due to heterozygous and homozygous forms of the D172N mutation. Mutant formulations were incorporated into multi-scale models. The blocking effects of chloroquine on ionic currents we

SUBMITTER: Luo C 

PROVIDER: S-EPMC5739752 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature