The sodium channel as a therapeutic target for prevention of lethal cardiac arrhythmias

European Coordinator:
  • Connie R. BEZZINA, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands)
North American Coordinator:
  • Mario DELMAR, New York University School of Medicine, New York, NY (USA)
  • Glenn FISHMAN, New York University School of Medicine (USA)
  • Alfred GEORGE, Northwestern University, Chicago (USA)
  • Casper HOOGENRAAD, Utrecht University (Netherlands)
  • Calum MacRAE, Brigham & Women’s Hospital, Boston (USA)
  • Arthur WILDE, Academic Medical Center, Amsterdam (Netherlands)

An irregular heartbeat, or arrhythmia, can often lead to dizziness, loss of consciousness or death. Indeed, 50% of all deaths from coronary artery disease (CAD) are related to sudden death, often because of an underlying cardiac arrhythmia. A normal heartbeat or rhythm is the result of a wave of electrical signal that spreads through cardiac cells in an organized and periodic manner. The response in each type of cardiac cell to the electrical stimulus is determined-in large part-by the sodium(Na) channel of the cell. Cardiac diseases such as CAD or heart failure, and certain genetic abnormalities, impact the normal function of the Na-channel; life threatening arrhythmias are therefore more common. To date, surprisingly little is known about the sodium channel, and why it is so susceptible to dysfunction in heart disease-despite it’s critical role in normal heart rhythm. This TNE will elucidate the composition and function of the Na-channel in each type of cardiac cell, and subsequently develop small molecules that can modify adversely altered channels. Their ultimate goal is to develop treatments that will prevent sudden cardiac death.