Ion Channels and Arrhythmias

Abnormal heart rhythms or arrhythmias, such as atrial fibrillation and ventricular fibrillation, are an important cause of disability and death. Atrial fibrillation is a common cause of blood clots that move to the brain to cause strokes, and ventricular fibrillation causes sudden death because the heart cannot produce an organized and effective contraction. Scientists in this area focus on the molecules by which heart cells communicate electrically and on how the conduction system that initiates and organizes the heartbeat is formed in the embryo and maintained in the adult. They study the molecular, cellular, genetic, and developmental mechanisms by which this system goes awry to cause arrhythmias. Pharmacogenomics, or how a drug can benefit one individual but harm another, is another area of investigation.

Some kinds of arrhythmias are inherited, and recent studies suggest that subtle mutations in genes important for formation of the heart in the embryo may cause rhythm disturbances in adults. Physicians studying patients with inherited atrial fibrillation work with geneticists, a developmental biologist studying formation of the cardiac conduction system, and an expert in ion channel regulation at the level of the cell and molecule to better understand this disorder.

The most deadly arrhythmias often involve the establishment of abnormal and constantly cycling “re-entry” circuits in the heart. Collaborations between cell and systems biologists, now being recruited, will determine how currents and channels can be manipulated to prevent the formation of abnormal circuits by making conduction more normal in diseased hearts. Animal modelers and electrophysiologists, in turn, will be able to test these hypotheses.