Genetics of acquired long QT syndrome
Dan M. Roden, Prakash C. Viswanathan
Dan M. Roden, Prakash C. Viswanathan
Published August 1, 2005
Citation Information: J Clin Invest. 2005;115(8):2025-2032. https://doi.org/10.1172/JCI25539.
View: Text | PDF
Review Series

Genetics of acquired long QT syndrome

Abstract

The QT interval is the electrocardiographic manifestation of ventricular repolarization, is variable under physiologic conditions, and is measurably prolonged by many drugs. Rarely, however, individuals with normal base-line intervals may display exaggerated QT interval prolongation, and the potentially fatal polymorphic ventricular tachycardia torsade de pointes, with drugs or other environmental stressors such as heart block or heart failure. This review summarizes the molecular and cellular mechanisms underlying this acquired or drug-induced form of long QT syndrome, describes approaches to the analysis of a role for DNA variants in the mediation of individual susceptibility, and proposes that these concepts may be generalizable to common acquired arrhythmias.

Authors

Dan M. Roden, Prakash C. Viswanathan

×

Figure 3

Options: View larger image (or click on image) Download as PowerPoint
Hypothesized molecular structure of the drug-binding site in the HERG ch...
Hypothesized molecular structure of the drug-binding site in the HERG channel. (A) The orientation of the channel pore, lined by S6 helices, is shown; drug access is via the intracellular face of the channel. Portions of 2 of the 4 subunits of the homotetrameric channel are shown, and the other 2 are omitted for clarity. The aromatic residues (tyrosine [Tyr] and phenylalanine [Phe]) that face the pore are thought to be high-affinity drug-binding sites. (B) Sequence comparisons between HERG and other potassium channels. With the exception of the closely related hEAG channel, the others have 1 or 2 prolines in S6 and 0 or 1 aromatic residues. As discussed in the text, these 2 features appear to determine the ease with which the HERG channel is blocked by a wide range of drugs. Adapted with permission from the Journal of Biological Chemistry (19).