Ginkgo biloba extract and ginkgolide antiarrhythmic potential by targeting hERG and ICa-L channel.
We investigated the effects of Ginkgo biloba extract (GBE) and ginkgolide (GLD) on human ether-a-go-go-related gene (hERG)-encoded K(+) channels and its underlying mechanisms in the hERG-HEK293 cell line by determining GBE- and GLD-induced changes in action potential duration (APD), L-type calcium currents (ICa-L), and the intracellular calcium concentration ([Ca(2+)]i) in guinea-pig ventricular myocytes. hERG currents, APD and ICa-L were recorded using the whole-cell patch clamp technique, the [Ca(2+)]i was examined by an immunofluorescence experiment. In the present study, we found that a low concentration of GBE (0.005 mg/ml) increased hERG currents, but the high concentration of GBE (from 0.05 to 0.25 mg/ml) reduced hERG currents. GLD reduced hERG currents in a concentration-dependent manner (from 0.005 to 0.25 mg/ml). Both GBE and GLD altered kinetics of the hERG channel. GBE accelerated the activation of hERG channels without changing the inactivation curve, but reduced the time constant of inactivation; GLD did not shift the activation or the inactivation curve, but only reduced the time constant of inactivation. Both GBE and GLD shortened the APD, inhibited the ICa-L currents, and decreased the [Ca(2+)]i in isolated guinea-pig ventricular myocytes. The results indicate that GBE and GLD can prevent ischemic arrhythmias and have an antiarrhythmic effect potential via inhibition of IKr and ICa-L currents.
Department of Pharmacology, Harbin Medical University, China.
Xin
X
Zhao
Hong
H
Yao
Hao-Lan
HL
Yin
Qi-Lei
QL
Zhu
Jia-Liang
JL
Sun
Wei
W
Ma
Yuan-Qi
YQ
Shi
Zhao-Guang
ZG
Liang
Bao-Xin
BX
Li
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics*; D020441:Ginkgo biloba; D046934:Ginkgolides / Q000494:pharmacology*; D006168:Guinea Pigs; D057809:HEK293 Cells; D006352:Heart Ventricles; D006801:Humans; D058990:Molecular Targeted Therapy; D032383:Myocytes, Cardiac / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D051638:Ether-A-Go-Go Potassium Channels; D046934:Ginkgolides; D010936:Plant Extracts; D002118:Calcium