Pharmacogenetics of Potassium Channel Blockers.
The QT interval on surface electrocardiograms provides a model of a multicomponent integrated readout of many biological systems, including ion channels, modulatory subunits, signaling systems that modulate their activity, and mechanisms that regulate the expression of their responsible genes. The problem of drug exposure causing exaggerated QT interval prolongation and torsades de pointes highlights the multicomponent nature of cardiac repolarization and the way in which simple perturbations can yield exaggerated responses. Future directions will involve cellular approaches coupled to evolving technologies that can interrogate multicellular systems and provide a sophisticated view of mechanisms in this previously idiosyncratic drug reaction.
Oates Institute for Experimental Therapeutics, Vanderbilt University School of Medicine, 1285 MRB IV, Nashville, TN 37232-0575, USA. Electronic address: dan.roden@vanderbilt.edu.
Dan M
DM
Roden
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D051379:Mice; D010597:Pharmacogenetics; D026902:Potassium Channel Blockers / Q000493:pharmacokinetics* / Q000627:therapeutic use*
D026902:Potassium Channel Blockers
Cardiac repolarization; Ion channels; Pharmacogenetics; Potassium channel blockers