title: Inhibitory effects of neferine on Nav1.5 channels expressed in HEK293 cells.
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.
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.|Department of Pharmacology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jun-Hua
authors.initials: JH
authors.lastname: Xiao
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jia-Ling
authors.initials: JL
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Ji-Zhou
authors.initials: JZ
authors.lastname: Xiang
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. tangqiang_tjmu@hust.edu.cn.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Tang
mesh_terms: D044182:Benzylisoquinolines / Q000008:administration & dosage*; D005786:Gene Expression Regulation / Q000187:drug effects*; D057809:HEK293 Cells; D006801:Humans; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000096:biosynthesis*; D018408:Patch-Clamp Techniques; D011802:Quinidine / Q000008:administration & dosage
chemical_list: D044182:Benzylisoquinolines; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; C057222:neferine; D011802:Quinidine
keywords: HEK293 cells; Nav1.5 channel; neferine; whole-cell patch-clamp