Details

Autor(en) / Beteiligte

• Zhao, Xu-yan
• Liu, Yu-qi
• Fu, Yi-cheng
• Xu, Bin
• Gao, Jin-liao
• Zheng, Xiao-qin
• Lin, Min
• Chen, Mei-yan
• Li, Yang

Titel

Frequency- and state-dependent blockade of human ether-a-go-go-related gene K^＋ channel by arecoline hydrobromide

Ist Teil von

• Chinese medical journal, 2012-03, Vol.125 (6), p.1068-1075

Ort / Verlag

China: Institute of Geriatric Cardiology, Chinese People's Liberation Army General Hospital, Beijing 100853, China

Erscheinungsjahr

2012

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Background The rapidly activating delayed rectifier potassium current （/Kr）, whose pore-forming alpha subunit is encoded by the human ether-a-go-go-related gene （hERG）, is a key contributor to the third phase of action potential repolarization. The aim of this study was to investigate the effect and mechanism of arecoline hydrobromide induced inhibition of hERG K^＋ current （/hERG）. Methods Transient transfection of hERG channel cDNA plasmid pcDNA3.1 into the cultured HEK293 cells was performed using Lipofectamine. A standard whole-cell patch-clamp technique was used to record the /hI=RG before and after the exposure to arecoline. Results Arecoline decreased the amplitude and the density of the /bERG in a concentration-dependent manner （IC5o=9.55 μmol/L）. At test potential of ＋60 mV, the magnitude of lhERG tail at test pulse of -40 mV was reduced from （151.7±6.2） pA/pF to （84.4±7.6） pA/pF （P 〈0.01, n=20） and the magnitude of IhERG tail at test pulse of -110 mV was reduced from （-187.5±9.8） pA/pF to （-97.6±12.6） pA/pF （P 〈0.01, n=20）. The blockade of arecoline in the open and inactivated state was significant in a state-dependent manner. The maximal blockade was achieved in the inactivated state. Studies of gating mechanism showed that the steady-state activation curve of IhERG was significantly negatively shifted by arecoline. Time constants of activation were shortened. Steady-state inactivation curve and time constants of fast inactivation were not significantly affected by arecoline. Furthermore, the inhibition of IhERG by arecoline was characterized markedly by a frequency-dependent manner from 0.03 to 1.00 Hz pulse. Conclusion Arecoline could potently block IhERG in both frequency and state-dependent manner.