Inhibitory effect of rhynchophylline on human ether-a-go-go related gene channel.
We studied the effects of Chinese traditional medicine rhynchophylline (Rhy) on human ether-a-go-go related gene (HERG) channel and characterized the electrophysiological properties of Rhy's pharmacological effect on HERG channel using Xenopus oocytes. Xenopus oocytes were injected with either 23 nl (5.75 ng) HERG cRNA or 23 nl distilled water. Xenopus oocytes were randomly assigned to receive one of the following different concentrations of Rhy: (1) control, (2)10 mumol/L Rhy, (3)100 mumol/L Rhy, (4) 500 mumol/L Rhy, (5) 1 000 mumol/L Rhy, (6) 10 000 mumol/L Rhy. Cell currents were recorded in oocytes. The peak tail currents of HERG channel were inhibited by Rhy. The inhibition was in a dose-dependent manner [IC(50)=(773.4 +/- 42.5) mumol/L]. Experiment with 100 mumol/L Rhy indicated that the degree of HERG blockade showed some voltage dependence (within -40 mV to -20 mV ). Kinetic analyses revealed that Rhy decreased the rate of channel activation. The findings indicate that Rhy inhibits HERG encoded potassium channels. It may underline the molecular mechanism of myocardial electrophysiological characteristics associated with this drug.
Gui
Le
L
Department of Cardiology, Affiliated Hospital, Nantong University, Nantong 226000, China.
Li
Zhi-Wang
ZW
Du
Rong
R
Yuan
Guo-Hui
GH
Li
Wei
W
Ren
Fa-Xin
FX
Li
Jing
J
Yang
Jun-Guo
JG
D000818:Animals; D003864:Depression, Chemical; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects* / Q000235:genetics*; D005260:Female; D006801:Humans; D026121:Indole Alkaloids / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects*; D000078183:Oxindoles; D018408:Patch-Clamp Techniques / Q000379:methods; D018075:RNA, Complementary / Q000235:genetics / Q000494:pharmacology; D014981:Xenopus
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D026121:Indole Alkaloids; C000606913:KCNH2 protein, human; D000078183:Oxindoles; D018075:RNA, Complementary; C052714:rhyncophylline