In silico assessment of genetic variation in KCNA5 reveals multiple mechanisms of human atrial arrhythmogenesis.

ABSTRACT: A recent experimental study investigating patients with lone atrial fibrillation identified six novel mutations in the KCNA5 gene. The mutants exhibited both gain- and loss-of-function of the atrial specific ultra-rapid delayed rectifier K+ current, IKur. The aim of this study is to elucidate and quantify the functional impact of these KCNA5 mutations on atrial electrical activity. A multi-scale model of the human atria was updated to incorporate detailed experimental data on IKur from both wild-type and mutants. The effects of the mutations on human atrial action potential and rate dependence were investigated at the cellular level. In tissue, we assessed the effects of the mutations on the vulnerability to unidirectional conduction patterns and dynamics of re-entrant excitation waves. Ga

SUBMITTER: Colman MA 

PROVIDER: S-EPMC5493429 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature