在多种动物中已发现作用于离子通道的蛋白，但在吸血节肢动物中却很少见。我们研究发现，印鼠客蚤唾液腺分泌多肽FS50含有蝎子β毒素典型的βαββ核心结构，且能特异性抑制Nav1.5和解救BaCl2诱发的大鼠心律失常。本项目拟在前期工作基础上，定点突变FS50分子表面疏水区、带电区和其他对药理活性重要区域的氨基酸，研究每个突变位点对FS50生物功能的影响，以期望找到FS50上决定生物功能的关键位点；定点突变Nav1.5上潜在的FS50结合位点，研究FS50对Nav1.5突变体电生理功能的影响，以期望找到FS50在Nav1.5上的结合位点及其抑制Nav1.5的分子机制；开展详细而全面的膜片钳分析来进一步确定FS50在Nav1.5上的结合位点及抑制机制；总之，我们希望揭示FS50抑制Nav1.5钠通道的结构基础和作用机制以便为其作为抗心律失常药物提供理论基础和指导。

Proteins affecting ion channels were reported from a lot of different spieces, while just few of them were from blood-feeding arthropods. We found that FS50 contained the calssical core βαββ of scorpin β toxin, and could inhibit specfically Nav1.5 and rescue rats from arrhythmia induced by BaCl2. Based on data obtained by us, we plan in this project to do the followings: First, to mutate crucial residues on FS50's molecular surface and analyse the mutants' function in order to find the bioactive determinant of FS50; Secondly, to mutate its potential binding sites in Nav1.5 and study the change of FS50 inhibiting Nav1.5 to discover the site and molecular mechanism of its interaction with Nav1.5; Thirdly, to carry on detailed patch clamp experiments to confirm the its binding site and molecular mechanism of interaction with Nav1.5. These research will help understand the structure basis and mechanism of FS50 inhibiting Nav1.5 and be used as theory basis and guide for FS50 as antiarrhythmia drugs.