title: hERG K(+) channels: structure, function, and clinical significance.
abstract: The human ether-a-go-go related gene (hERG) encodes the pore-forming subunit of the rapid component of the delayed rectifier K(+) channel, Kv11.1, which are expressed in the heart, various brain regions, smooth muscle cells, endocrine cells, and a wide range of tumor cell lines. However, it is the role that Kv11.1 channels play in the heart that has been best characterized, for two main reasons. First, it is the gene product involved in chromosome 7-associated long QT syndrome (LQTS), an inherited disorder associated with a markedly increased risk of ventricular arrhythmias and sudden cardiac death. Second, blockade of Kv11.1, by a wide range of prescription medications, causes drug-induced QT prolongation with an increase in risk of sudden cardiac arrest. In the first part of this review, the properties of Kv11.1 channels, including biogenesis, trafficking, gating, and pharmacology are discussed, while the second part focuses on the pathophysiology of Kv11.1 channels.
authors.affiliation: Mark Cowley Lidwill Research Programme in Cardiac Electrophysiology, Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia. j.vandenberg@victorchang.edu.au
authors.forename: Jamie I
authors.initials: JI
authors.lastname: Vandenberg
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Perry
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Perrin
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Mann
authors.forename: Ying
authors.initials: Y
authors.lastname: Ke
authors.forename: Adam P
authors.initials: AP
authors.lastname: Hill
mesh_terms: D000818:Animals; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006329:Heart Conduction System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D015640:Ion Channel Gating; D008133:Long QT Syndrome / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D010641:Phenotype; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011487:Protein Conformation; D021381:Protein Transport; D013329:Structure-Activity Relationship
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D026902:Potassium Channel Blockers; D011188:Potassium