Journal
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS
Volume 23, Issue 2, Pages 119-129Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/1074248417729880
Keywords
potassium channels; repolarization; physiological mechanisms; currents; ion channel; drug target
Funding
- Fundamental Research Grant Scheme, Ministry of Education, Malaysia [FRGS/2/2014/SKK01/PERDANA/02/1]
- Research Support Fund, Faculty of Health and Medical Science, University of Surrey
- Physiological Society, United Kingdom
- Wellcome Trust
- Medical Research Council
- British Heart Foundation
- McVeigh Benefaction
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The development of novel drugs specifically directed at the ion channels underlying particular features of cardiac action potential (AP) initiation, recovery, and refractoriness would contribute to an optimized approach to antiarrhythmic therapy that minimizes potential cardiac and extracardiac toxicity. Of these, K+ channels contribute numerous and diverse currents with specific actions on different phases in the time course of AP repolarization. These features and their site-specific distribution make particular K+ channel types attractive therapeutic targets for the development of pharmacological agents attempting antiarrhythmic therapy in conditions such as atrial fibrillation. However, progress in the development of such temporally and spatially selective antiarrhythmic drugs against particular ion channels has been relatively limited, particularly in view of our incomplete understanding of the complex physiological roles and interactions of the various ionic currents. This review summarizes the physiological properties of the main cardiac potassium channels and the way in which they modulate cardiac electrical activity and then critiques a number of available potential antiarrhythmic drugs directed at them.
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