PMID- 15548530 OWN - NLM STAT- MEDLINE DCOM- 20050513 LR - 20210206 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 280 IP - 13 DP - 2005 Apr 1 TI - Jingzhaotoxin-I, a novel spider neurotoxin preferentially inhibiting cardiac sodium channel inactivation. PG - 12069-76 AB - Jingzhaotoxin-I (JZTX-I), a 33-residue polypeptide, is derived from the Chinese tarantula Chilobrachys jing-zhao venom based on its ability to evidently increase the strength and the rate of vertebrate heartbeats. The toxin has three disulfide bonds with the linkage of I-IV, II-V, and III-VI that is a typical pattern found in inhibitor cystine knot molecules. Its cDNA determined by rapid amplification of 3'- and 5'-cDNA ends encoded a 62-residue precursor with a small proregion of eight residues. Whole-cell configuration indicated that JZTX-I was a novel neurotoxin preferentially inhibiting cardiac sodium channel inactivation by binding to receptor site 3. Although JZTX-I also exhibits the interaction with channel isoforms expressing in mammalian and insect sensory neurons, its affinity for tetrodotoxin-resistant subtype in mammalian cardiac myocytes (IC50 = 31.6 nm) is approximately 30-fold higher than that for tetrodotoxin-sensitive subtypes in latter tissues. Not affecting outward delay-rectified potassium channels expressed in Xenopus laevis oocytes and tetrodotoxin-resistant sodium channels in mammal sensory neurons, JZTX-I hopefully represents a potent ligand to discriminate cardiac sodium channels from neuronal tetrodotoxin-resistant isoforms. Furthermore, different from any reported spider toxins, the toxin neither modifies the current-voltage relationships nor shifts the steady-state inactivation of sodium channels. Therefore, JZTX-I defines a new subclass of spider sodium channel toxins. JZTX-I is an alpha-like toxin first reported from spider venoms. The result provides an important witness for a convergent functional evolution between spider and other animal venoms. FAU - Xiao, Yucheng AU - Xiao Y AD - College of Life Sciences, Hunan Normal University, Changsha 410081, China. FAU - Tang, Jianzhou AU - Tang J FAU - Hu, Weijun AU - Hu W FAU - Xie, Jinyun AU - Xie J FAU - Maertens, Chantal AU - Maertens C FAU - Tytgat, Jan AU - Tytgat J FAU - Liang, Songping AU - Liang S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20041117 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (DNA, Complementary) RN - 0 (Disulfides) RN - 0 (Ligands) RN - 0 (Neurotoxins) RN - 0 (Peptides) RN - 0 (Potassium Channels) RN - 0 (Protein Isoforms) RN - 0 (Sodium Channel Blockers) RN - 0 (Sodium Channels) RN - 0 (Spider Venoms) RN - 0 (jingzhaotoxin-I, Chilobrachys jingzhao) RN - 4368-28-9 (Tetrodotoxin) SB - IM MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - Cells, Cultured MH - Cloning, Molecular MH - DNA, Complementary/metabolism MH - Disulfides/chemistry MH - Dose-Response Relationship, Drug MH - Evolution, Molecular MH - Female MH - Inhibitory Concentration 50 MH - Insecta MH - Ligands MH - Male MH - Membrane Potentials MH - Molecular Sequence Data MH - Myocardium/metabolism MH - Myocytes, Cardiac/drug effects/metabolism MH - Neurons/drug effects/metabolism MH - Neurotoxins/chemistry MH - Oocytes/drug effects/metabolism MH - Peptides/*chemistry/pharmacology MH - Phylogeny MH - Potassium Channels/chemistry MH - Protein Isoforms MH - Rats MH - Rats, Sprague-Dawley MH - Sequence Analysis, DNA MH - Sequence Homology, Amino Acid MH - Sodium Channel Blockers/*pharmacology MH - Sodium Channels/*chemistry/metabolism MH - Spider Venoms/*chemistry/pharmacology MH - Spiders MH - Tetrodotoxin/chemistry MH - Time Factors MH - Xenopus laevis EDAT- 2004/11/19 09:00 MHDA- 2005/05/14 09:00 CRDT- 2004/11/19 09:00 PHST- 2004/11/19 09:00 [pubmed] PHST- 2005/05/14 09:00 [medline] PHST- 2004/11/19 09:00 [entrez] AID - S0021-9258(19)60528-4 [pii] AID - 10.1074/jbc.M411651200 [doi] PST - ppublish SO - J Biol Chem. 2005 Apr 1;280(13):12069-76. doi: 10.1074/jbc.M411651200. Epub 2004 Nov 17.