[Evaluation of pro-arrhythmic risk of drugs due to QT interval prolongation by the HERG expression system].
Recently, there has been considerable attention focused on drugs that prolong the QT interval of the electrocardiogram. This occasionally evolves to fetal, polymorphic ventricular arrhythmias, torsades de pointes. Therefore, the early detection of the risk of drug-induced QT prolongation is important for avoiding the adverse cardiovascular effect in clinical use. It has been suggested that the QT prolongation and ventricular arrhythmia caused by drugs might be secondary to their ability to interfere with cardiac potassium channels involved in action potential repolarization and in particular with rapidly activating delayed rectifier K+ current (IKr). In cardiac myocytes, IKr contributes to termination of the plateau phase of action potential. The ether-a-go-go related gene in humans expressed a K+ channel current with biophysical characteristics similar to those of IKr. Electrophysiological studies on cloned HERG channels can provide fundamental information concerning the cardiac safety profile of new developing drugs.
Chachin
Motohiko
M
Department of Pharmacology II, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan. CHACHIN@boehringer-ingelheim.co.jp
Kurachi
Yoshihisa
Y
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D027682:Cation Transport Proteins; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D018014:Gene Transfer Techniques; D006801:Humans; D066298:In Vitro Techniques; D008133:Long QT Syndrome / Q000139:chemically induced*; D015221:Potassium Channels / Q000187:drug effects* / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D014981:Xenopus
D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG