Long QT syndrome: biophysical and pharmacologic mechanisms in LQT3.
The congenital long QT syndromes (LQTSs) are a group of inherited cardiac disorders that increase the risk of sudden death from ventricular arrhythmias. Individuals with LQTS show abnormalities in cardiac repolarization. Mutations that cause LQTSs are distributed throughout the human genome on chromosomes 3, 4, 7, 11, and 21. Recent molecular genetic studies established that LQT3 results from mutations in the cardiac sodium ion channel gene (SCN5A). Research efforts are aimed at elucidating molecular mechanisms, determining the links between clinical phenotypes and the individual gene mutations, and pharmacologic targeting of the phenotypes. This approach will ultimately guide rational therapy. In addition, LQT3 serves as a model for inherited molecular-based disorders, as well as a paradigm for understanding the genesis and control of other cardiac arrhythmias.
Merck Research Laboratories, West Point, Pennsylvania 19486, USA. paul_bennett@merck.com
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D006801:Humans; D008133:Long QT Syndrome / Q000503:physiopathology*; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel; D015222:Sodium Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels