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.
Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Science, Hunan Normal University, Changsha 410081, PR China.
Meichi
M
Wang
Qingping
Q
Liu
Haiyong
H
Luo
Jiang
J
Li
Jianzhou
J
Tang
Yucheng
Y
Xiao
Songping
S
Liang
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