中文摘要：

敬钊毒素-Ⅲ（Jingzhaotoxin-Ⅲ,JZTX-Ⅲ）是从敬钊缨毛蛛毒液中分离到的一种门控调节型毒素,能选择性抑制钠通道亚型Nav1.5激活,但对其他6种钠通道亚型（Nav1.1~Nav1.4、Nav1.6和Nav1.7）无抑制作用。为了更好地研究钠通道结构与功能之间的关系,采用全细胞膜片钳技术检测了JZTX-Ⅲ对表达在ND7/23细胞上的Nav1.8通道的影响。结果显示,JZTX-Ⅲ抑制Nav1.8电流,并且这种抑制作用具有时间和浓度依赖性,抑制时间常数和IC50值分别为41.15±0.6 s和1.4±0.23μmol/L;1μmol/L JZTX-Ⅲ使Nav1.8通道的电流-电压关系曲线和激活曲线分别向去极化方向漂移10 mV和9 mV,使Nav1.8通道的稳态失活曲线向超极化方向漂移16 mV,明显改变Nav1.8通道的激活和稳态失活动力学。此外,钠通道序列比对结果提示JZTX-Ⅲ可能通过结合Nav1.8通道DIIS3~S4连接环上的Lys（K）残基抑制Nav1.8通道。以上研究结果为进一步探索钠通道结构与功能之间的关系奠定了基础。

英文摘要：

Jingzhaotoxin-Ⅲ （JZTX-Ⅲ） is a gating modifier toxin isolated from Chinese tarantula Chilobrachys jingzhao venom. The toxin can selectively inhibit the activation of Nav1.5 channel, but has no inhibition effect on other sodium channel subtypes including Nav1.1-Nav1.4, Nav1.6 and Nav1.7. in order to better understand the structure-function relationships of sodium channels, the effects of JZTX-Ⅲ on Navl.8 channels expressed in ND7/23 cells were analyzed using the whole cell patch-clamp technique. The results showed that JZTX-Ⅲ could inhibit the currents of Navl.8 channel in a time- and concentration-dependent manner. The time constant for JZTX-Ⅲ inhibition was 41.15±0.6 s and the IC5o value was 1.4±0.23 μmol/L. The ap- plication of 1 μmol/L JZTX-Ⅲ caused a depolarized shift of the current-voltage relationship curve and acti- vation curve by approximate 10 mV and 9 mV, respectively. Furthermore, the steady-state inactivation curve was hyperpolarizingly shifted by 16 inV. Therefore, JZTX-Ⅲ could affect the activation and inactivation characteristics of Navl.8 channels. What＇s more, amino acid sequence alignment implied that JZTX-Ⅲ might inhibit Navl.8 channel by binding to the residue Lys（K） in the DIIS3-S4 linker of Navl.8 channel. The findings will facilitate further investigation of the structure-function relationships of sodium channels.