title: HERG K+ channel blockade by the novel antiviral drug sophocarpine.
abstract: Human ether-à-go-go-related gene (HERG) encodes the rapid component of the cardiac delayed rectifier K+ current, which has an important role in the repolarization of the cardiac action potential. QT interval prolongation through HERG channel inhibition is associated with a risk of torsade de pointes arrhythmias and is a major challenge for drug development. The effects of the novel antiviral drug sophocarpine (SC) were examined on stably expressed HERG channels in human embryonic kidney (HEK293) cells using a whole-cell patch clamp technique, Western blot analysis and immunofluorescence experiments. SC inhibited HERG channels in a concentration-dependent manner, with an IC50 of 100-300 microM. SC significantly accelerated channel inactivation, recovery from inactivation and onset of inactivation. In addition, it had no effect on channel activation and deactivation. Based on Western blot and immunofluorescence results, SC had no significant effect on the expression of HERG protein. In summary, SC is a potent blocker of HERG K+ channels that functions by changing the channel inactivation kinetics. In addition, SC has no effect on the generation and trafficking of HERG protein.
authors: Department of Pharmacology, Harbin Medical University, 194 Xuefu Road, Harbin 150081, China.
authors: Xue-Ling
authors: XL
authors: Zhao
authors: Zhi-Ping
authors: ZP
authors: Qi
authors: Cheng
authors: C
authors: Fang
authors: Ming-Hong
authors: MH
authors: Chen
authors: Yan-Jie
authors: YJ
authors: Lv
authors: Bao-Xin
authors: BX
authors: Li
authors: Bao-Feng
authors: BF
authors: Yang
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D000072237:ERG1 Potassium Channel; D004591:Electrophoresis, Polyacrylamide Gel; D004594:Electrophysiology; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000502:physiology; D006801:Humans; D007700:Kinetics; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D000093842:Matrines
chemical_list: D000470:Alkaloids; D000998:Antiviral Agents; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D026902:Potassium Channel Blockers; C000606913:KCNH2 protein, human; C035933:sophocarpine; D000093842:Matrines