Europace Advance Access published online on July 24, 2008
Europace, doi:10.1093/europace/eun193
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REVIEW
Role of potassium currents in cardiac arrhythmias
1 Department of Pharmacology and Toxicology, Medical Faculty, Dresden University of Technology, Dresden, Germany; 2 Centro Interuniversitario di Medicina Molecolare, University of Florence, Florence, Italy
Abnormal excitability of myocardial cells may give rise to ectopic beats and initiate re-entry around an anatomical or functional obstacle. As K+ currents control the repolarization process of the cardiac action potential (AP), the K+ channel function determines membrane potential and refractoriness of the myocardium. Both gain and loss of the K+ channel function can lead to arrhythmia. The former because abbreviation of the active potential duration (APD) shortens refractoriness and wave length, and thereby facilitates re-entry and the latter because excessive prolongation of APD may lead to torsades de pointes (TdP) arrhythmia and sudden cardiac death. The pro-arrhythmic consequences of malfunctioning K+ channels in ventricular and atrial tissue are discussed in the light of three pathophysiologically relevant aspects: genetic background, drug action, and disease-induced remodelling. In the ventricles, loss-of-function mutations in the genes encoding for K+ channels and many drugs (mainly hERG channel blockers) are related to hereditary and acquired long-QT syndrome, respectively, that put individuals at high risk for developing TdP arrhythmias and life-threatening ventricular fibrillation. Similarly, down-regulation of K+ channels in heart failure also increases the risk for sudden cardiac death. Mutations and polymorphisms in genes encoding for atrial K+ channels can be associated with gain-of-function and shortened, or with loss-of-function and prolonged APs. The block of atrial K+ channels becomes a particular therapeutic challenge when trying to ameliorate atrial fibrillation (AF). This arrhythmia has a strong tendency to cause electrical remodelling, which affects many K+ channels. Atrial-selective drugs for the treatment of AF without affecting the ventricles could target structures such as IKur or constitutively active IK,ACh channels.
Key Words: Potassium channels, Ventricular fibrillation, Torsades de pointes, Atrial fibrillation, Genetic polymorphism, Drugs, Remodelling
* Corresponding author: Institut für Pharmakologie und Toxikologie, Fetscherstr. 74, 01307 Dresden, Germany. Tel: +49 351 4586300; fax: +49 351 4586315.E-mail address: ravens{at}rcs.urz.tu-dresden.de
Manuscript submitted 29 April 2008. Accepted after revision 4 July 2008.
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