Veratridine modifies the gating of human voltage-gated sodium channel Nav1.7  

作　　者：Xiao-yu Zhang Rui-yun Bi Peng Zhang Ye-hua Gan 

机构地区：[1]Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China [2]The Third Dental Center, Peking University School and Hospital of Stomatology,Beijing 100081, China

出　　处：《Acta Pharmacologica Sinica》2018年第11期1716-1724,共9页中国药理学报（英文版）

摘　　要：Veratridine is a lipid-soluble neurotoxin derived from plants in the family Liliaceae. it has been broadly investigated for its action as a sodium channel agonist However, the effects of veratridine on subtypes of sodium channels, especially Nav1.7, remain to be studied. Here, we investigated the effects of veratridine on human Nav1.7 ectopically expressed in HEK293A cells and recorded Nay1.7 currents from the cells using whole-cell patch clamp technique. We found that veratridine exerted a dose-dependent inhibitory effect on the peak current of Navl.7, with the half-maximal inhibition concentration （IC50） of 18.39 μM. Meanwhile, veratridine also elicited tail current （linearly） and sustained current [half-maximal concentration （EC50）： 9.53 μM], also in a dose- dependent manner. Veratridine （75 μM） shifted the half-maximal activation voltage of the Nav1.7 activation curve in the hyperpolarized direction, from -21.64 ± 0.75 mV to -28.14 ± 0.66 mV, and shifted the half-inactivation voltage of the steady-state inactivation curve from -59.39 ± 0.39 mV to -73.78 ± 0.5 mV. An increased frequency of stimulation decreased the peak and tail currents of Navl.7 for each pulse along with pulse number, and increased the accumulated tail current at the end of train stimulation. These findings reveal the different modulatory effects of veratridine on the Nav1.7 peak current and tail current.Veratridine is a lipid-soluble neurotoxin derived from plants in the family Liliaceae. it has been broadly investigated for its action as a sodium channel agonist However, the effects of veratridine on subtypes of sodium channels, especially Nav1.7, remain to be studied. Here, we investigated the effects of veratridine on human Nav1.7 ectopically expressed in HEK293A cells and recorded Nay1.7 currents from the cells using whole-cell patch clamp technique. We found that veratridine exerted a dose-dependent inhibitory effect on the peak current of Navl.7, with the half-maximal inhibition concentration （IC50） of 18.39 μM. Meanwhile, veratridine also elicited tail current （linearly） and sustained current [half-maximal concentration （EC50）： 9.53 μM], also in a dose- dependent manner. Veratridine （75 μM） shifted the half-maximal activation voltage of the Nav1.7 activation curve in the hyperpolarized direction, from -21.64 ± 0.75 mV to -28.14 ± 0.66 mV, and shifted the half-inactivation voltage of the steady-state inactivation curve from -59.39 ± 0.39 mV to -73.78 ± 0.5 mV. An increased frequency of stimulation decreased the peak and tail currents of Navl.7 for each pulse along with pulse number, and increased the accumulated tail current at the end of train stimulation. These findings reveal the different modulatory effects of veratridine on the Nav1.7 peak current and tail current.

关 键 词：VERATRIDINE Nay1.7 channel activation channel inactivation ELECTROPHYSIOLOGY HEK293 cells 

分 类 号：Q73[生物学—分子生物学] U455.4[建筑科学—桥梁与隧道工程]