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.
Keywords: Sarcolemmal and mitochondrial ATP-sensitive potassium channels, cardiac arrhythmias, pharmacological modulators.
Current Pharmaceutical Design
Title:ATP-Sensitive Potassium Channel Modulators and Cardiac Arrhythmias: An Update
Volume: 21 Issue: 8
Author(s): Danina M. Muntean, Lorand Kiss, Norbert Jost and Istvan Baczko
Affiliation:
Keywords: Sarcolemmal and mitochondrial ATP-sensitive potassium channels, cardiac arrhythmias, pharmacological modulators.
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.
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Cite this article as:
Muntean Danina M., Kiss Lorand, Jost Norbert and Baczko Istvan, ATP-Sensitive Potassium Channel Modulators and Cardiac Arrhythmias: An Update, Current Pharmaceutical Design 2015; 21 (8) . https://dx.doi.org/10.2174/1381612820666141029102800
DOI https://dx.doi.org/10.2174/1381612820666141029102800 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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