Computational Analysis of the Mode of Action of Disopyramide and Quinidine on hERG-Linked Short QT Syndrome in Human Ventricles.

ABSTRACT: The short QT syndrome (SQTS) is a rare cardiac disorder associated with arrhythmias and sudden death. Gain-of-function mutations to potassium channels mediating the rapid delayed rectifier current, I_Kr, underlie SQTS variant 1 (SQT1), in which treatment with Na⁺ and K⁺ channel blocking class Ia anti-arrhythmic agents has demonstrated some efficacy. This study used computational modeling to gain mechanistic insights into the actions of two such drugs, disopyramide and quinidine, in the setting of SQT1. The O'Hara-Rudy (ORd) human ventricle model was modified to incorporate a Markov chain formulation of I_Kr describing wild type (WT) and SQT1 mutant conditions. Effects of multi-channel block by disopyramide and quinidine, including bin

SUBMITTER: Whittaker DG 

PROVIDER: S-EPMC5649182 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature