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Jingzhaotoxin-II, a novel tarantula toxin preferentially targets rat cardiac sodium channel.
Biochem Pharmacol. 2008 Dec 15; 76(12):1716-27.BP

Abstract

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.

Authors+Show Affiliations

Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, College of Life Science, Hunan Normal University, Changsha 410081, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18840410

Citation

Wang, Meichi, et al. "Jingzhaotoxin-II, a Novel Tarantula Toxin Preferentially Targets Rat Cardiac Sodium Channel." Biochemical Pharmacology, vol. 76, no. 12, 2008, pp. 1716-27.
Wang M, Liu Q, Luo H, et al. Jingzhaotoxin-II, a novel tarantula toxin preferentially targets rat cardiac sodium channel. Biochem Pharmacol. 2008;76(12):1716-27.
Wang, M., Liu, Q., Luo, H., Li, J., Tang, J., Xiao, Y., & Liang, S. (2008). Jingzhaotoxin-II, a novel tarantula toxin preferentially targets rat cardiac sodium channel. Biochemical Pharmacology, 76(12), 1716-27. https://doi.org/10.1016/j.bcp.2008.09.008
Wang M, et al. Jingzhaotoxin-II, a Novel Tarantula Toxin Preferentially Targets Rat Cardiac Sodium Channel. Biochem Pharmacol. 2008 Dec 15;76(12):1716-27. PubMed PMID: 18840410.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Jingzhaotoxin-II, a novel tarantula toxin preferentially targets rat cardiac sodium channel. AU - Wang,Meichi, AU - Liu,Qingping, AU - Luo,Haiyong, AU - Li,Jiang, AU - Tang,Jianzhou, AU - Xiao,Yucheng, AU - Liang,Songping, Y1 - 2008/09/17/ PY - 2008/07/20/received PY - 2008/09/04/revised PY - 2008/09/05/accepted PY - 2008/10/9/pubmed PY - 2008/12/25/medline PY - 2008/10/9/entrez SP - 1716 EP - 27 JF - Biochemical pharmacology JO - Biochem Pharmacol VL - 76 IS - 12 N2 - 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. SN - 1873-2968 UR - https://www.unboundmedicine.com/medline/citation/18840410/Jingzhaotoxin_II_a_novel_tarantula_toxin_preferentially_targets_rat_cardiac_sodium_channel_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-2952(08)00635-7 DB - PRIME DP - Unbound Medicine ER -