Inhibitory effects of neferine on Nav1.5 channels expressed in HEK293 cells.
10.1007/s11596-016-1613-8
- Author:
Chen WANG
1
;
Huan WANG
1
;
Jun-Hua XIAO
1
;
Jia-Ling WANG
1
;
Ji-Zhou XIANG
1
;
Qiang TANG
2
Author Information
1. Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
2. Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. tangqiang_tjmu@hust.edu.cn.
- Publication Type:Journal Article
- Keywords:
HEK293 cells;
Nav1.5 channel;
neferine;
whole-cell patch-clamp
- MeSH:
Benzylisoquinolines;
administration & dosage;
Gene Expression Regulation;
drug effects;
HEK293 Cells;
Humans;
NAV1.5 Voltage-Gated Sodium Channel;
biosynthesis;
Patch-Clamp Techniques;
Quinidine;
administration & dosage
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2016;36(4):487-493
- CountryChina
- Language:English
-
Abstract:
Neferine, a bisbenzylisoquinoline alkaloid in Lotus Plumule, was proved to have a wide range of biological activities. In the present study, using whole-cell patch-clamp technique, we investigated the effects of neferine on Nav1.5 channels that are stably expressed in HEK 293 cells. We found that neferine potently and reversibly inhibited Nav1.5 currents in a concentration dependent manner with a half-maximal inhibition (IC50) being 26.15 μmol/L. The inhibitory effects of neferine on Nav1.5 currents were weaker than those of quinidine at the same concentration. The steady-state inactivation curve was significantly shifted towards hyperpolarizing direction in the presence of 30 μmol/L neferine, while the voltage-dependent activation was unaltered. Neferine prolonged the time to peak of activation, increased the inactivation time constants of Nav1.5 currents and markedly slowed the recovery from inactivation. The inhibitory effect of neferine could be potentiated in a frequency-dependent manner. These results suggested that neferine can block Nav1.5 channels under the open state and inactivating state and it is an open channel blocker of Nav1.5 channels.
