For instance, Kv4.3, Kv4.2, and Kv1.4 conduct the transient outward currents (I to), and Kv7.1 (KvLQTS), Kv11.1 (hERG), and Kv1.5 conduct the slowly, rapidly, and ultrarapidly activating outward rectifying currents I Ks, I Kr, and I Kur, respectively (see ref. Inward current is predominantly conducted via L-type Ca 2+ channels (I Ca,L), whereas multiple K + channels contribute to outward current. The cardiac action potential (AP) differs from that of other excitable tissues by a prominent plateau phase resulting from fine tuning of depolarizing inward and repolarizing outward currents. Current evidence suggests that pure I Kur channel block may not be sufficient to suppress AF.Ītrial fibrillation, Electrical remodelling, Kv1.5, I Kur, Atrial selective drugs 1. Some new compounds developed as I Kur blockers are described and their efficacy in treatment of atrial fibrillation (AF) is discussed. Investigation of I Kur channel blockers in cardiomyocytes is complicated (i) by substantial overlap of I Kur with other currents, notably the transient outward current I to, (ii) by lack of drug selectivity, and (iii) by disease-induced regulation of I Kur. The ion conducting pore of the channel is formed by four Kv1.5 α-subunits, whereas the ancillary β-subunits Kvβ1.2, Kvβ1.3, and Kvβ2.1 control channel trafficking and plasma membrane integration as well as activation and inactivation kinetics. Here we provide an overview of the properties of I Kur channels in expression systems and native cardiomyocytes. Thus, I Kur channel blockers are expected to prolong selectively the atrial effective refractory period without inducing proarrhythmic effects due to excessive ventricular action potential prolongation.
The ultrarapid delayed rectifier channels have attracted considerable interest as targets for ‘atrial-selective’ antiarrhythmic drugs because they contribute to atrial but not to ventricular repolarization.
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