Long QT syndrome: novel insights into the mechanisms of cardiac arrhythmias
Robert S. Kass, Arthur J. Moss
Robert S. Kass, Arthur J. Moss
Published September 15, 2003
Citation Information: J Clin Invest. 2003;112(6):810-815. https://doi.org/10.1172/JCI19844.
View: Text | PDF
Science in Medicine

Long QT syndrome: novel insights into the mechanisms of cardiac arrhythmias

Abstract

The congenital long QT syndrome is a rare disorder in which mutation carriers are at risk for polymorphic ventricular tachycardia and/or sudden cardiac death. Discovery and analysis of gene mutations associated with variants of this disorder have provided novel insight into mechanisms of cardiac arrhythmia and have raised the possibility of mutation-specific therapeutic intervention.

Authors

Robert S. Kass, Arthur J. Moss

×

Figure 2

Options: View larger image (or click on image) Download as PowerPoint
Disruption of local signaling domains occurs in LQT-1 syndrome. Stimulat...
Disruption of local signaling domains occurs in LQT-1 syndrome. Stimulation of β-adrenergic receptors (β-ARs) in the heart leads to PKA-dependent phosphorylation of multiple intracellular targets in cardiac myocytes. These targets include the ryanodine receptor (RyR2), L-type calcium channels, and the KCNQ1/KCNE1 K+ channel. In response to stress in healthy patients, β-AR stimulation results in phosphorylation of all three of these targets and uniform electrical activity on the ECG (upper ECG). When the KCNQ1/KCNE1 complex is disrupted by an inherited mutation, an unbalanced cellular response occurs, which leads to dysfunctional rhythm (lower ECG). Modified with permission from ref. 27. SR, sarcoplasmic reticulum; VGCC, voltage-gated calcium channel.