ω-Agatoxin IVA TFA

ω-Agatoxin IVA TFA是ω-Agatoxin IVA（CAS 号 145017-83-0）的三氟乙酸盐形式。ω-Agatoxin IVA是源自漏斗网蜘蛛毒液的肽类毒素，核心生物功能为特异性阻断 P/Q 型电压门控钙通道（Cav2.1），对 N 型钙通道有弱阻断作用（1μM 时部分抑制），对 L、T 型钙通道无影响，可抑制神经递质（谷氨酸、GABA）释放、发挥抗癫痫与神经保护效应，还能介导心脏迷走神经元的烟碱能激活调控；IC50 具有亚型 / 剪接变体特异性，对 P 型 Cav2.1（无 NP motif）为 1-2 nM，对 Q 型 Cav2.1（含 NP motif）升至 270.5±1.1 nM，整体 IC50 范围 2-1000 nM；常用应用浓度：体外细胞实验 100 nM-1μM（如神经元钙电流记录、突触传递研究），动物实验颅内注射 0.01-1 nM（急性癫痫模型）、腹腔注射 0.1-0.5 nM（癫痫点燃模型），EEG 监测癫痫放电用 0.5 nM；有效治疗浓度对应动物模型，0.5 nM 颅内注射可显著延长癫痫发作潜伏期，0.1-0.5 nM 腹腔注射能抑制癫痫进展、减少脑内凋亡（降低 cleaved caspase-3）并升高 BDNF 表达，且不影响运动协调。

参考文献：

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[5] Ryu JH, Jung HJ, Konishi S, Kim HH, Park ZY, Kim JI. Structure-activity relationships of ω-Agatoxin IVA in lipid membranes. Biochem Biophys Res Commun. 2017 Jan 1;482(1):170-175. doi: 10.1016/j.bbrc.2016.11.025. Epub 2016 Nov 9. PMID: 27838299.

[6] Singh M, Sapkota K, Sakimura K, Kano M, Cowell RM, Overstreet-Wadiche L, Hablitz JJ, Nakazawa K. Maturation of GABAergic Synaptic Transmission From Neocortical Parvalbumin Interneurons Involves N-methyl-D-aspartate Receptor Recruitment of Cav2.1 Channels. Neuroscience. 2023 Mar 1;513:38-53. doi: 10.1016/j.neuroscience.2023.01.007. Epub 2023 Jan 20. PMID: 36682446.

[7] Inan SY, Yildirim S, Tanriover G, Ilhan B. P/Q type (Cav2.1) Calcium Channel Blocker ω-Agatoxin IVA Alters Cleaved Caspase-3 and BDNF Expressions in the Rat Brain and Suppresses Seizure Activity. Mol Neurobiol. 2024 Apr;61(4):1861-1872. doi: 10.1007/s12035-023-03678-0. Epub 2023 Oct 6. PMID: 37798599.

[8] Li Z, Cong Y, Wu T, Wang T, Lou X, Yang X, Yan N. Structural basis for different ω-agatoxin IVA sensitivities of the P-type and Q-type Cav2.1 channels. Cell Res. 2024 Jun;34(6):455-457. doi: 10.1038/s41422-024-00940-5. Epub 2024 Mar 5. PMID: 38443561; PMCID: PMC11143261.