The ion channel basis of pharmacological effects of amiodarone on myocardial electrophysiological properties, a comprehensive review

• Published in: Biomedicine & pharmacotherapy Vol. 174; p. 116513
• Main Authors: Gelman, Illia, Sharma, Neelakshi, Mckeeman, Olivia, Lee, Peter, Campagna, Noah, Tomei, Nicole, Baranchuk, Adrian, Zhang, Shetuan, El-Diasty, Mohammad
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.05.2024; Elsevier
• Subjects: Action Potentials - drug effects; Amiodarone; Amiodarone - pharmacology; Animals; Anti-Arrhythmia Agents - pharmacology; Anti-Arrhythmia Agents - therapeutic use; Anti-arrhythmic drugs; Cardiac electrophysiology; Electropharmacology; Electrophysiological Phenomena - drug effects; Humans; Ion channels; Ion Channels - drug effects; Ion Channels - metabolism; Long QT Syndrome - chemically induced; Long QT Syndrome - drug therapy; Long QT Syndrome - physiopathology; Myocardium - metabolism; Anti-arrhythmic drugs; Ion channels; Amiodarone; Electropharmacology; Cardiac electrophysiology
• ISSN: 0753-3322; 1950-6007; 1950-6007
• DOI: 10.1016/j.biopha.2024.116513

Amiodarone is a benzofuran-based class III antiarrhythmic agent frequently used for the treatment of atrial and ventricular arrhythmias. The primary target of class III antiarrhythmic drugs is the cardiac human ether-a-go-go-related gene (hERG) encoded channel, KCNH2, commonly known as HERG, that conducts the rapidly activating delayed rectifier potassium current (IKr). Like other class III antiarrhythmic drugs, amiodarone exerts its physiologic effects mainly through IKr blockade, delaying the repolarization phase of the action potential and extending the effective refractory period. However, while many class III antiarrhythmics, including sotalol and dofetilide, can cause long QT syndrome (LQTS) that can progress to torsade de pointes, amiodarone displays less risk of inducing this fatal arrhythmia. This review article discusses the arrhythmogenesis in LQTS from the aspects of the development of early afterdepolarizations (EADs) associated with Ca2+ current, transmural dispersion of repolarization (TDR), as well as reverse use dependence associated with class III antiarrhythmic drugs to highlight electropharmacological effects of amiodarone on the myocardium.