title: Pharmacology of voltage-gated potassium channel Kv1.5--impact on cardiac excitability.
abstract: Voltage activated potassium (Kv) channels are intensely investigated targets within the pharmacological strategies to treat cardiac arrhythmia. For atrial fibrillation (AF) substances inhibiting the ultra rapid outward rectifying Kv current (IKur) and its underlying Kv1.5 channel have been developed. Here we describe potential limitations of this approach with respect to critical parameters of Kv channel pharmacology. In healthy tissue IKur/Kv1.5 inhibition can unexpectedly lead to action potential shortening with corresponding arrhythmogenic effects. In tissue with chronic AF, electrical remodeling occurs which is accompanied with changes in ion channel expression and composition. As a consequence atrial tissue exhibits a different pharmacological fingerprint. New strategies to obtain more mechanistic insight into drug target interaction are needed for better understanding the pharmacological potential of IKur/Kv1.5 inhibition for AF treatment.
authors.affiliation: Department of Pharmacology and Toxicology, Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus, Fetscherstraße 74, 01307 Dresden, Germany.
authors.forename: Erich
authors.initials: E
authors.lastname: Wettwer
authors.affiliation: Institute of Physiology, University of Kiel, Hermann-Rodewald-Straße 5, 24118 Kiel, Germany. Electronic address: h.terlau@physiologie.uni-kiel.de.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Terlau
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D051666:Kv1.5 Potassium Channel / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D051666:Kv1.5 Potassium Channel