Mitochondria and arrhythmias.
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.
Lifespan Cardiovascular Institute, Providence VA Medical Center, and Brown University, Providence, RI 02903, USA.
Kai-Chien
KC
Yang
Department of Medicine/Cardiology, University of Illinois at Chicago, Chicago, IL 60612, USA; Department of Pathology, and University of Illinois at Chicago, Chicago, IL 60612, USA; Department of Pharmacology, University of Illinois at Chicago, Chicago, IL 60612, USA.
Marcelo G
MG
Bonini
Lifespan Cardiovascular Institute, Providence VA Medical Center, and Brown University, Providence, RI 02903, USA. Electronic address: samuel_dudley@brown.edu.
Samuel C
SC
Dudley
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002316:Cardiotonic Agents / Q000627:therapeutic use; D006801:Humans; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D015221:Potassium Channels / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism
D000975:Antioxidants; D015220:Calcium Channels; D002316:Cardiotonic Agents; D015221:Potassium Channels; D017382:Reactive Oxygen Species; D015222:Sodium Channels; D000255:Adenosine Triphosphate; D002118:Calcium
Calcium; Free radicals; Heart; Ion channels; Reactive oxygen species; Sudden death