Arrhythmia formation in subclinical ("silent") long QT syndrome requires multiple insults: quantitative mechanistic study using the KCNQ1 mutation Q357R as example.

ABSTRACT:

Background

In subclinical or silent long QT syndrome, the QT interval is normal under basal conditions. The hypothesis that insults to the repolarization reserve may cause arrhythmias in silent mutation carriers but not in noncarriers has been proposed as a general principle, yet crucial aspects remain descriptive, lacking quantification.

Objective

To utilize accurate mathematical models of the human action potential and β-adrenergic stimulation to quantitatively investigate arrhythmia-formation mechanisms peculiar to silent long QT syndrome, using mutation Q357R in KCNQ1 (α subunit of slow-delayed rectifier I(Ks)) as a paradigm.

Methods

Markov models were formulated to account for altered I(Ks) kinetics in Q357R compared with wild type and introduced into a detailed

SUBMITTER: O'Hara T 

PROVIDER: S-EPMC3443981 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature