title: ATP-sensitive potassium channel modulators and cardiac arrhythmias: an update.
abstract: Ischemia and heart failure-related cardiac arrhythmias, both atrial (e.g., atrial fibrillation) and ventricular (e.g., malignant tachyarrhythmias) represent a leading cause of morbidity and mortality worldwide. Despite the progress made in the last decade in understanding their pathophysiological mechanisms there is still an unmet need for safer and more efficacious pharmacological treatment, especially when considering the drawbacks and complications of implantable devices. Cardiac ATP-sensitive potassium channels located in the sarcolemmal membrane (sarcKATP) and the inner mitochondrial membrane (mitoKATP) have emerged as crucial controllers of several key cellular functions. In the past three decades a tremendous amount of research led to their structural and functional characterization unveiling both a protective role in cardiac adaptive responses to metabolic stress and a seemingly paradoxical role in promoting as well as protecting against atrial and ventricular arrhythmias. On the other hand, several KATP inhibitors have emerged as potential ischemia selective antiarrhythmic drugs. In this respect, cardioselective, chamber specific and combined sarcKATP and mitoKATP modulators currently represent a promising field for drug development.
authors.forename: Danina M
authors.initials: DM
authors.lastname: Muntean
authors.forename: Loránd
authors.initials: L
authors.lastname: Kiss
authors.forename: Norbert
authors.initials: N
authors.lastname: Jost
authors.affiliation: Department of Pathophysiology, "Victor Babes" University of Medicine and Pharmacy, Faculty of Medicine, 2, Eftimie Murgu Sq., 300041 Timisoara, RO. jost.norbert@umft.ro.
authors.forename: István
authors.initials: I
authors.lastname: Baczko
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000503:physiopathology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D054086:KATP Channels / Q000187:drug effects* / Q000502:physiology; D012508:Sarcolemma / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship
chemical_list: D000889:Anti-Arrhythmia Agents; D054086:KATP Channels