ATP-Sensitive Potassium Channel Modulators and Cardiac Arrhythmias an Update /

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 m...

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Bibliographic Details
Main Authors: Muntean Danina M.
Kiss Loránd
Jost Norbert László
Baczkó István
Format: Article
Published: Bentham Science Publishers Ltd. 2015
Series:CURRENT PHARMACEUTICAL DESIGN 21 No. 8
doi:10.2174/1381612820666141029102800

mtmt:2763902
Online Access:http://publicatio.bibl.u-szeged.hu/9910
Description
Summary: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.
Physical Description:1091-1102
ISSN:1381-6128