Jingzhaotoxin-II, a novel tarantula toxin preferentially targets rat cardiac sodium channel.
Naturally occurring toxins are invaluable tools for exploration of the structure and function relationships of voltage-gated sodium channels (VGSCs). In this study, we isolated and characterized a novel VGSC toxin named jingzhaotoxin-II (JZTX-II) from the tarantula Chilobrachys jingzhao venom. JZTX-II consists of 32 amino acid residues including two acidic and two basic residues. Cloned and sequenced using 3'- and 5'-rapid amplification of the cDNA ends, the full-length cDNA for JZTX-II was found to encode a 63-residue precursor which contained a signal peptide of 21 residues, a propeptide of 10 residues and a mature peptide of 32 residues. Under whole-cell voltage-clamp conditions, JZTX-II significantly slowed rapid inactivation of TTX-resistant (TTX-R) VGSC on cardiac myocytes with the IC50=0.26+/-0.09 microM. In addition, JZTX-II had no effect on TTX-R VGSCs on rat dorsal root ganglion neurons but exerted a concentration-dependent reduction in tetrodotoxin-sensitive (TTX-S) VGSCs accompanied by a slowing of sodium current inactivation similar to delta-ACTXs. It is notable that TTX-S VGSCs on cultured rat hippocampal neurons were resistant to JZTX-II at high dose. Based on its high selectivity for mammalian VGSC subtypes, JZTX-II might be an important ligand for discrimination of VGSC subtypes and for exploration of the distribution and modulation mechanisms of VGSCs.
Wang
Meichi
M
Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Science, Hunan Normal University, Changsha 410081, PR China.
Liu
Qingping
Q
Luo
Haiyong
H
Li
Jiang
J
Tang
Jianzhou
J
Xiao
Yucheng
Y
Liang
Songping
S
D000818:Animals; D003001:Cloning, Molecular; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000166:cytology; D006624:Hippocampus / Q000166:cytology; D032383:Myocytes, Cardiac / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects; D021382:Protein Sorting Signals; D051381:Rats; D017422:Sequence Analysis, DNA; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects*; D013111:Spider Venoms / Q000235:genetics / Q000494:pharmacology*; D013112:Spiders
D004365:Drugs, Chinese Herbal; D021382:Protein Sorting Signals; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013111:Spider Venoms; C533889:jingzhaotoxin-II, Chilobrachys jingzhao; C511008:jingzhiguanxin