Pro‐arrhythmogenic effects of the S140G KCNQ1 mutation in human atrial fibrillation – insights from modelling

•  A previous study has identified a gene mutation (KCNQ1 S140G) in some patients with a familial form of atrial fibrillation, one of the most common cardiac rhythm disturbances causing morbidity and mortality. A causal link between the mutation and genesis of atrial fibrillation has not yet been directly demonstrated. •  Increased IKs arising from the KCNQ1 S140G mutation abbreviated atrial action potential duration (APD) and effective refractory period (ERP) and flattened APD and ERP restitution curves. It reduced atrial conduction velocity at low excitation rates, but increased it at high excitation rates that facilitated the conduction of high rate atrial excitation waves. •  The mutation increased tissue susceptibility for initiation and maintenance of atrial arrhythmias. •  The mutation stabilizes and accelerates re‐entrant excitation waves, leading to rapid and sustained re‐entry. •  This study provides novel insights towards understanding the mechanisms underlying the pro‐arrhythmic effects of the KCNQ1 S140G mutation.