title: KCNE4 and KCNE5: K(+) channel regulation and cardiac arrhythmogenesis.
abstract: KCNE proteins are single transmembrane-segment voltage-gated potassium (Kv) channel ancillary subunits that exhibit a diverse range of physiological functions. Human KCNE gene mutations are associated with various pathophysiological states, most notably cardiac arrhythmias. Of the five isoforms in the human KCNE gene family, KCNE4 and the X-linked KCNE5 are, to date, the least-studied. Recently, however, interest in these neglected genes has been stoked by their putative association with debilitating or lethal cardiac arrhythmias. The sometimes-overlapping functional effects of KCNE4 and KCNE5 vary depending on both their Kv α subunit partner and on other ancillary subunits within the channel complex, but mostly fall into two contrasting categories - either inhibition, or fine-tuning of gating kinetics. This review covers current knowledge regarding the molecular mechanisms of KCNE4 and KCNE5 function, human disease associations, and findings from very recent studies of cardiovascular pathophysiology in Kcne4(-/-) mice.
authors.affiliation: Bioelectricity Laboratory, Dept. of Pharmacology and Dept. of Physiology and Biophysics, School of Medicine, University of California, Irvine, CA, USA. Electronic address: abbottg@uci.edu.
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Abbott
mesh_terms: D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics* / Q000503:physiopathology; D006339:Heart Rate; D006801:Humans; D015640:Ion Channel Gating; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism*
chemical_list: C498897:KCNE4 protein, human; C502068:KCNE5 protein, human; D024642:Potassium Channels, Voltage-Gated
keywords: AMME contiguous gene syndrome; Atrial fibrillation; Brugada syndrome; Cardiac arrhythmia; KCNQ1; Long QT syndrome; Potassium channel