Jingzhaotoxin-III – Ion Channels and Transporters

Jingzhaotoxin-III (ß-TRTX-Cj1α) has been isolated initially from the Chinese Tarantula spider Chilobrachys Jingzhaovenom. Jingzhaotoxin-III selectively inhibits the activation of the voltage-dependent sodium channel Nav1.5 in heart or cancer cells with an IC50value close to 350 nM. It is inactive on Nav1.2, Nav1.4, Nav1.6 and Nav1.7 and should therefore be considered as an interesting research tool to discriminate between sodium channel subtypes. Jingzhaotoxin-III binds onto receptor site 4 presumably located on DIIS3-S4 linker of Nav1.5 and supposedly blocks Nav1.5 through a different mechanism than ProTx-II and Huwentoxin IV. ß-TRTX-Cj1α is composed of 36 amino acid residues including 6 cysteines cross-linked according to a C1-C4, C2-C5 and C3-C6 pattern. Jingzhaotoxin-III also inhibits Kv2.1 channel with an IC50 of around 700 nM.

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