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Jingzhaotoxin-III, a novel spider toxin inhibiting activation of voltage-gated sodium channel in rat cardiac myocytes.
J Biol Chem. 2004 Jun 18; 279(25):26220-6.JB

Abstract

We have isolated a cardiotoxin, denoted jingzhaotoxin-III (JZTX-III), from the venom of the Chinese spider Chilobrachys jingzhao. The toxin contains 36 residues stabilized by three intracellular disulfide bridges (I-IV, II-V, and III-VI), assigned by a chemical strategy of partial reduction and sequence analysis. Cloned and sequenced using 3'-rapid amplification of cDNA ends and 5'-rapid amplification of cDNA ends, the full-length cDNA encoded a 63-residue precursor of JZTX-III. Different from other spider peptides, it contains an uncommon endoproteolytic site (-X-Ser-) anterior to mature protein and the intervening regions of 5 residues, which is the smallest in spider toxin cDNAs identified to date. Under whole cell recording, JZTX-III showed no effects on voltage-gated sodium channels (VGSCs) or calcium channels in dorsal root ganglion neurons, whereas it significantly inhibited tetrodotoxin-resistant VGSCs with an IC(50) value of 0.38 microm in rat cardiac myocytes. Different from scorpion beta-toxins, it caused a 10-mV depolarizing shift in the channel activation threshold. The binding site for JZTX-III on VGSCs is further suggested to be site 4 with a simple competitive assay, which at 10 microm eliminated the slowing currents induced by Buthus martensi Karsch I (BMK-I, scorpion alpha-like toxin) completely. JZTX-III shows higher selectivity for VGSC isoforms than other spider toxins affecting VGSCs, and the toxin hopefully represents an important ligand for discriminating cardiac VGSC subtype.

Authors+Show Affiliations

College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, People's Republic of China.No affiliation info availableNo 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

15084603

Citation

Xiao, Yucheng, et al. "Jingzhaotoxin-III, a Novel Spider Toxin Inhibiting Activation of Voltage-gated Sodium Channel in Rat Cardiac Myocytes." The Journal of Biological Chemistry, vol. 279, no. 25, 2004, pp. 26220-6.
Xiao Y, Tang J, Yang Y, et al. Jingzhaotoxin-III, a novel spider toxin inhibiting activation of voltage-gated sodium channel in rat cardiac myocytes. J Biol Chem. 2004;279(25):26220-6.
Xiao, Y., Tang, J., Yang, Y., Wang, M., Hu, W., Xie, J., Zeng, X., & Liang, S. (2004). Jingzhaotoxin-III, a novel spider toxin inhibiting activation of voltage-gated sodium channel in rat cardiac myocytes. The Journal of Biological Chemistry, 279(25), 26220-6.
Xiao Y, et al. Jingzhaotoxin-III, a Novel Spider Toxin Inhibiting Activation of Voltage-gated Sodium Channel in Rat Cardiac Myocytes. J Biol Chem. 2004 Jun 18;279(25):26220-6. PubMed PMID: 15084603.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Jingzhaotoxin-III, a novel spider toxin inhibiting activation of voltage-gated sodium channel in rat cardiac myocytes. AU - Xiao,Yucheng, AU - Tang,Jianzhou, AU - Yang,Yuejun, AU - Wang,Meichi, AU - Hu,Weijun, AU - Xie,Jinyun, AU - Zeng,Xiongzhi, AU - Liang,Songping, Y1 - 2004/04/14/ PY - 2004/4/16/pubmed PY - 2004/7/24/medline PY - 2004/4/16/entrez SP - 26220 EP - 6 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 279 IS - 25 N2 - We have isolated a cardiotoxin, denoted jingzhaotoxin-III (JZTX-III), from the venom of the Chinese spider Chilobrachys jingzhao. The toxin contains 36 residues stabilized by three intracellular disulfide bridges (I-IV, II-V, and III-VI), assigned by a chemical strategy of partial reduction and sequence analysis. Cloned and sequenced using 3'-rapid amplification of cDNA ends and 5'-rapid amplification of cDNA ends, the full-length cDNA encoded a 63-residue precursor of JZTX-III. Different from other spider peptides, it contains an uncommon endoproteolytic site (-X-Ser-) anterior to mature protein and the intervening regions of 5 residues, which is the smallest in spider toxin cDNAs identified to date. Under whole cell recording, JZTX-III showed no effects on voltage-gated sodium channels (VGSCs) or calcium channels in dorsal root ganglion neurons, whereas it significantly inhibited tetrodotoxin-resistant VGSCs with an IC(50) value of 0.38 microm in rat cardiac myocytes. Different from scorpion beta-toxins, it caused a 10-mV depolarizing shift in the channel activation threshold. The binding site for JZTX-III on VGSCs is further suggested to be site 4 with a simple competitive assay, which at 10 microm eliminated the slowing currents induced by Buthus martensi Karsch I (BMK-I, scorpion alpha-like toxin) completely. JZTX-III shows higher selectivity for VGSC isoforms than other spider toxins affecting VGSCs, and the toxin hopefully represents an important ligand for discriminating cardiac VGSC subtype. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/15084603/Jingzhaotoxin_III_a_novel_spider_toxin_inhibiting_activation_of_voltage_gated_sodium_channel_in_rat_cardiac_myocytes_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=15084603 DB - PRIME DP - Unbound Medicine ER -