title: Translational toxicology and rescue strategies of the hERG channel dysfunction: biochemical and molecular mechanistic aspects.
abstract: The human ether-à-go-go related gene (hERG) potassium channel is an obligatory anti-target for drug development on account of its essential role in cardiac repolarization and its close association with arrhythmia. Diverse drugs have been removed from the market owing to their inhibitory activity on the hERG channel and their contribution to acquired long QT syndrome (LQTS). Moreover, mutations that cause hERG channel dysfunction may induce congenital LQTS. Recently, an increasing number of biochemical and molecular mechanisms underlying hERG-associated LQTS have been reported. In fact, numerous potential biochemical and molecular rescue strategies are hidden within the biogenesis and regulating network. So far, rescue strategies of hERG channel dysfunction and LQTS mainly include activators, blockers, and molecules that interfere with specific links and other mechanisms. The aim of this review is to discuss the rescue strategies based on hERG channel toxicology from the biochemical and molecular perspectives.
authors.affiliation: 1] Department of Pharmacology, Harbin Medical University, Harbin, China [2] The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China (Key Laboratory of Cardiovascular Research, Ministry of Education), China.
authors.forename: Kai-ping
authors.initials: KP
authors.lastname: Zhang
authors.affiliation: 1] Department of Pharmacology, Harbin Medical University, Harbin, China [2] The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China (Key Laboratory of Cardiovascular Research, Ministry of Education), China.
authors.forename: Bao-feng
authors.initials: BF
authors.lastname: Yang
authors.affiliation: 1] Department of Pharmacology, Harbin Medical University, Harbin, China [2] The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China (Key Laboratory of Cardiovascular Research, Ministry of Education), China.
authors.forename: Bao-xin
authors.initials: BX
authors.lastname: Li
mesh_terms: D000818:Animals; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009154:Mutation; D010641:Phenotype; D021381:Protein Transport; D018570:Risk Assessment; D015398:Signal Transduction / Q000187:drug effects; D014116:Toxicology; D057170:Translational Research, Biomedical
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human