Inherited cardiac arrhythmia syndromes: what have they taught us about arrhythmias and anti-arrhythmic therapy?
1. In recent years, the identification of the gene defects in a vast array of monogenic disorders has revolutionized our understanding of the basic mechanisms underlying numerous disease processes. 2. Mutations in cardiac ion channels have been identified as the basis of a wide range of inherited arrhythmia syndromes, including the congenital long QT syndromes, Brugada syndrome, Lenegre syndrome, Andersen's disease and familial atrial fibrillation. 3. Identification of mutations in the human-ether-a-go-go-related gene (HERG) K(+) channel as the molecular basis of congenital long QT syndrome type 2 also led to the discovery that HERG is the molecular target for the vast majority of drugs (both cardiac and non-cardiac) that cause drug-induced arrhythmias. This has had profound implications not only for the development of anti-arrhythmic agents, but also for drug development in general. 4. The sequencing of the human genome in a sense represents the pinnacle of the reductionist era of molecular medicine. The great challenge now is to re-integrate the information gathered during the 'reductionist era' to provide a better understanding of the intact organism. Computer modelling is likely to be a key component of that re-integration process.
Subbiah
Rajesh N
RN
Electrophysiology and Biophysics Program, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales 21010, Australia.
Campbell
Terence J
TJ
Vandenberg
Jamie I
JI
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D013577:Syndrome
D000889:Anti-Arrhythmia Agents