Back to Search
Start Over
Jingzhaotoxin-III, a Novel Spider Toxin Inhibiting Action of Voltage-gated Sodium Channel in Rat Cardiac Myocytes.
- Source :
-
Journal of Biological Chemistry . 6/18/2004, Vol. 279 Issue 25, p26220-26226. 7p. - Publication Year :
- 2004
-
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 IC50 value of 0.38 μM in rat cardiac myocytes. Different from scorpion β-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 μM eliminated the slowing currents induced by Buthus martensi Karsch I (BMK-I, scorpion α-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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 279
- Issue :
- 25
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 13828035
- Full Text :
- https://doi.org/10.1074/jbc.M401387200