Predicting changes to I from missense mutations in human SCN5A.

Mutations in SCN5A can alter the cardiac sodium current I and increase the risk of potentially lethal conditions such as Brugada and long-QT syndromes. The relation between mutations and their clinical phenotypes is complex, and systems to predict clinical severity of unclassified SCN5A variants perform poorly. We investigated if instead we could predict changes to I, leaving the link from I to clinical phenotype for mechanistic simulation studies.

Electromechanical window negativity in genotyped long-QT syndrome patients: relation to arrhythmia risk.

Aim: Prolonged and dispersed left-ventricular (LV) contraction is present in patients with long-QT syndrome (LQTS). Electrical and mechanical abnormalities appear most pronounced in symptomatic individuals. We focus on the 'electromechanical window' (EMW; duration of LV-mechanical systole minus QT interval) in patients with genotyped LQTS.

Long-QT mutation p.K557E-Kv7.1: dominant-negative suppression of IKs, but preserved cAMP-dependent up-regulation.

Aims: Mutations in KCNQ1, encoding for Kv7.1, the α-subunit of the IKs channel, cause long-QT syndrome type 1, potentially predisposing patients to ventricular tachyarrhythmias and sudden cardiac death, in particular, during elevated sympathetic tone. Here, we aim at characterizing the p.