JZTX-IV, a unique acidic sodium channel toxin isolated from the spider Chilobrachys jingzhao.
Neurotoxins are important tools to explore the structure and function relationship of different ion channels. From the venom of Chinese spider Chilobrachys jingzhao, a novel toxin, Jingzhaotoxin-IV (JZTX-IV), is isolated and characterized. It consists of 34 amino acid residues including six acidic residues clustered with negative charge (pI=4.29). The full-length cDNA of JZTX-IV encodes an 86-amino acid precursor containing a signal peptide of 21 residues, a mature peptide of 34 residues and an intervening sequence of 29 residues with terminal Lys-Gly as the signal of amidation. Under whole-cell patch clamp conditions, JZTX-IV inhibits current and slows the inactivation of sodium channels by shifting the voltage dependence of activation to more depolarized potentials on DRG neurons, therefore, differs from the classic site 4 toxins that shift voltage dependence of activation in the opposite direction. In addition, JZTX-IV shows a slowing inactivation of sodium channel with a hyperpolarizing shift of the steady-state inactivation on acutely isolated rat cardiac cell and DRG neurons, differs from the classic site 3 toxins that do not affect the steady-state of inactivation. At high concentration, JZTX-IV has no significant effect on tetrodotoxin-resistant (TTX-R) sodium channels on rat DRG neurons and tetrodotoxin-sensitive (TTX-S) sodium channels on hippocampal neurons. Our data establish that, contrary to known toxins, JZTX-IV neither binds to the previously characterized classic site 4, nor site 3 by modifying channel gating, thus making it a novel probe of channel gating in sodium channels with potential to shed new light on this process.
Wang
Meichi
M
Key Laboratory of Protein Chemistry and Developmental Biology of the Ministry of Education, The College of Life Science, Hunan Normal University, Lushan Road, Yuelu District, Changsha, Hunan 410081, China.
Diao
Jianbo
J
Li
Jiang
J
Tang
Jianzhou
J
Lin
Yin
Y
Hu
Weijun
W
Zhang
Yongqun
Y
Xiao
Yucheng
Y
Liang
Songping
S
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects; D008297:Male; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D009498:Neurotoxins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020539:Sequence Analysis, Protein; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology; D013111:Spider Venoms / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D013112:Spiders / Q000235:genetics / Q000378:metabolism*
D009498:Neurotoxins; D010455:Peptides; D015222:Sodium Channels; D013111:Spider Venoms; C538991:jingzhaotoxin-IV, Chilobrachys jingzhao