The novel mechanism of oxymatrine affecting HERG currents at different temperatures.
OBJECTIVE
Human ether-à-go-go-related gene (hERG) has an important role in the repolarization of the cardiac action potential. Our studies were to investigate the effects of oxymatrine (one of the natural constituents extracted from Chinese herb Sophora flavescens Ait) on hERG-encoded K(+) channels at different temperatures and its underlying mechanism.


METHODS
The effects of oxymatrine were examined on hERG channels stably expressed in HEK293 cells using a whole-cell patch clamp technique.


RESULTS
At the temperature 30°C, oxymatrine inhibited hERG current in a concentration-dependent manner and the IC(50) was ∼665 μM. However at the temperature of 20°C, low concentration oxymatrine C≤100 μM increased hERG current density. However, high concentration oxymatrine C>100 μM inhibited the hERG current density significantly. Oxymatrine only affected the activation kinetic of hERG channels at all temperatures and had a high binding affinity for open state of hERG channels except the 300 μM-20°C group which had a high binding affinity for inactive state of hERG channels.


CONCLUSIONS
Oxymatrine is a low potency blocker of hERG K+ channels at 30°C, low concentration oxymatrine affect the hERG activation gating with accelerating hERG tail current at 20°C, oxymatrine is a potential hERG activator at low temperatures.
Department of Pharmacology, Harbin Medical University, Harbin, China.
Mei-Qin
MQ
Hu
Zeng-Xiang
ZX
Dong
Wen-Xiao
WX
Zhao
Jing
J
Sun
Xin
X
Zhao
Dong-Fang
DF
Gu
Yan
Y
Zhang
Bao-Xin
BX
Li
Bao-Feng
BF
Yang
D000470:Alkaloids / Q000494:pharmacology*; D055724:Electrophysiological Phenomena; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D007700:Kinetics; D018408:Patch-Clamp Techniques; D011485:Protein Binding; D011807:Quinolizines / Q000494:pharmacology*; D013696:Temperature; D000093842:Matrines
D000470:Alkaloids; D051638:Ether-A-Go-Go Potassium Channels; D011807:Quinolizines; C037573:oxymatrine; D000093842:Matrines