Mechanism of Proarrhythmic Effects of Potassium Channel Blockers.
Any disturbance of electrical impulse formation in the heart and of impulse conduction or action potential (AP) repolarization can lead to rhythm disorders. Potassium (K(+)) channels play a prominent role in the AP repolarization process. In this review we describe the causes and mechanisms of proarrhythmic effects that arise as a response to blockers of cardiac K(+) channels. The largest and chemically most diverse groups of compound targets are Kv11.1 (hERG) and Kv7.1 (KvLQT1) channels. Finally, the proarrhythmic propensity of atrial-selective K(+) blockers inhibiting Kv1.5, Kir3.1/3.4, SK, and K2P channels is discussed.
Danish Arrhythmia Research Centre, Faculty of Health and Medical Sciences, University of Copenhagen, 3 Blegdamsvej, 3 Copenhagen N DK-2200, Denmark.
Lasse
L
Skibsbye
Department of Pharmacology and Toxicology, Medical Faculty Carl Gustav Carus, Institut für Pharmakologie und Toxikologie, TU Dresden, Fetscherstrasse 74, Dresden D-01307, Germany. Electronic address: ravens@mail.zih.tu-dresden.de.
Ursula
U
Ravens
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000188:drug therapy; D006329:Heart Conduction System / Q000187:drug effects*; D006801:Humans; D051379:Mice; D026902:Potassium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use
D000889:Anti-Arrhythmia Agents; D026902:Potassium Channel Blockers
Antiarrhythmic drugs; Cardiac action potentials; K(+) channels blockers; Mechanism of arrhythmia; Proarrhythmic effects