title: Role of potassium currents in cardiac arrhythmias.
abstract: 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 I(Kur) or constitutively active I(K,ACh) channels.
authors.affiliation: Department of Pharmacology and Toxicology, Medical Faculty, Dresden University of Technology, Dresden, Germany. ravens@rcs.urz.tu-dresden.de
authors.forename: Ursula
authors.initials: U
authors.lastname: Ravens
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cerbai
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D006329:Heart Conduction System / Q000503:physiopathology*; D006801:Humans; D015640:Ion Channel Gating; D009200:Myocardial Contraction; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels
chemical_list: D015221:Potassium Channels; D011188:Potassium