PubMed 18774108

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kv1.5

Title: Can inhibition of IKur promote atrial fibrillation?

Authors: Alexander Burashnikov, Charles Antzelevitch

Journal, date & volume: , 2008 Sep , 5, 1304-9

PubMed link:

Block of ultrarapid delayed rectified potassium current (I(Kur)), present in atria but not in ventricles, is thought to be a promising approach for atrial-specific therapy of atrial fibrillation (AF). However, it has been shown that I(Kur) block may abbreviate atrial repolarization and that loss-of-function mutations in KCNA5, which encodes K(v) 1.5 channels responsible for I(Kur), is associated with familial AF.Our objective in this study was to use low concentrations of 4-aminopyridine (4-AP, 10 to 50 microM), known to selectively block I(Kur), to assess the proarrhythmic and antiarrhythmic effects of I(Kur) block in healthy and remodeled atria.Isolated canine coronary-perfused right atrial preparations were used. Acetylcholine or ischemia/reperfusion was used to acutely remodel the atria. Transmembrane action potentials and a pseudo-electrocardiogram were simultaneously recorded.Normal (healthy) atria typically displayed action potentials (AP) with a prominent plateau, whereas remodeled atria displayed triangular-shaped APs (remodeled). In healthy atria, in which AF could not be induced with programmed stimulation, 4-AP abbreviated action potential measured at 90% repolarization (APD(90)) and effective refractory period (ERP), permitting the induction of AF in 4 of 12 preparations (33%). In remodeled atria, 4-AP produced little (50 microM) to no (10 to 25 microM) prolongation of APD(90) or ERP and was either ineffective or poorly effective in terminating AF or preventing its induction.Our findings suggest that block of I(Kur) can provide the substrate for development of AF in healthy canine atria, presumably via abbreviation of APD and ERP.