Cardiac Ultrarapid Delayed Rectifiers

Abstract
Classical cardiac delayed rectifier currents activate at least two orders of magnitude slower than delayed rectifier currents in nerve and skeletal muscle tissue. It has recently become evident that many cardiac tissues express delayed rectifier currents with kinetics similar to those of nerve and muscle. These currents have been designated IKur (for ‘ultrarapid’ delayed rectifier), in contrast to the classical cardiac rapid (IKr) and slow (IKs) delayed rectifier components. Although the kinetics of IKur in different species and tissues are similar, their pharmacological properties vary greatly. It now appears that the differences among various IKurs are due to differences in the molecular basis. A variety of Shaker-related clones (Kv1.2, 1.5, 2.1 and 3.1) that form IKur channels upon heterologous expression have been identified with specific IKurs (e.g. Kv1.2, rat atrium; Kv1.5, mouse ventricle and human atrium; Kv3.1, dog atrium). The present article reviews the distribution, biophysical and pharmacological properties, molecular basis and functional role of IKur, as well as the potential value of IKur as a target for new antiarrhythmic drug development.