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 Nav1.7 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 Nav1.7, 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 Nav1.7 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.

中文翻译：

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Veratridine修饰人电压门控钠通道Nav1.7的门控。

Veratridine是源自百合科植物的脂溶性神经毒素。已经对其作为钠通道激动剂的作用进行了广泛的研究。然而，维甲酸对钠通道亚型的影响，尤其是Nav1.7，仍有待研究。在这里，我们研究了维他命啶对HEK293A细胞中异位表达的人Nav1.7的影响，并使用全细胞膜片钳技术记录了细胞中的Nav1.7电流。我们发现维拉替丁对Nav1.7的峰值电流具有剂量依赖性的抑制作用，最大抑制浓度（IC ₅₀）的一半为18.39 µM。同时，维他命啶还引起尾电流（线性地）和持续电流[半最大浓度（EC ₅₀）：9.53 µM]，也呈剂量依赖性。Veratridine（75 µM）使Nav1.7激活曲线的半最大激活电压在超极化方向上从-21.64±0.75 mV移至-28.14±0.66 mV，并使稳态灭活的半灭活电压移动曲线从-59.39±0.39 mV到-73.78±0.5 mV。刺激频率的增加降低了每个脉冲的Nav1.7的峰值和尾电流以及脉冲数，并增加了列车刺激结束时累积的尾电流。这些发现揭示了维拉替丁对Nav1.7峰值电流和尾电流的不同调节作用。