Abstract
Mitochondria are essential to providing ATP, thereby satisfying the energy demand of the incessant electrical activity and contractile action of cardiac muscle. Emerging evidence indicates that mitochondrial dysfunction can adversely affect cardiac electrical functioning by impairing the intracellular ion homeostasis and membrane excitability through reduced ATP production and excessive reactive oxygen species (ROS) generation, resulting in increased propensity to cardiac arrhythmias. In this review, the molecular mechanisms linking mitochondrial dysfunction to cardiac arrhythmias are discussed with an emphasis on the impact of increased mitochondrial ROS on the cardiac ion channels and transporters that are critical to maintaining normal electromechanical functioning of the cardiomyocytes. The potential of using mitochondria-targeted antioxidants as a novel antiarrhythmia therapy is highlighted.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 351-361 |
| Number of pages | 11 |
| Journal | Free Radical Biology and Medicine |
| Volume | 71 |
| DOIs | |
| State | Published - Jun 2014 |
| Externally published | Yes |
Bibliographical note
Funding Information:This work was funded by National Institutes of Health Grants RO1 HL104025 (S.C.D.) and HL106592 (S.C.D.), Veterans Affairs MERIT Grant BX000859 (S.C.D.), and American Heart Association Midwest Affiliation Postdoctoral Fellowship AHA13POST14380029 (K.C.Y.); Dr. Bonini is funded by the American Heart Association ( 13GRNT16400010 ; 09SDG2250933 ) and the U.S. Department of Defense W911NF-12-1-0493 ). Dr. Dudley is an inventor of 13/551,790 “A Method for Ameliorating or Preventing Arrhythmic Risk Associated with Cardiomyopathy by Improving Conduction Velocity” and 13/507,319 “A Method for Modulating or Controlling Connexin43 (Cx43) Level of a Cell and Reducing Arrhythmic Risk.”
Keywords
- Calcium
- Free radicals
- Heart
- Ion channels
- Reactive oxygen species
- Sudden death