title: Jingzhaotoxin-35, a novel gating-modifier toxin targeting both Nav1.5 and Kv2.1 channels.
abstract: Jingzhaotoxin-35 (JZTX-35), a 36-residue polypeptide, was purified from the venom of the Chinese tarantula Chilobrachys jingzhao. JZTX-35 inhibited Nav1.5 and Kv2.1 currents with the IC50 value of 1.07 μM and 3.62 μM, respectively, but showed no significant effect on either Na(+) currents or Ca(2+) currents evoked in hippocampal neurons. It shifted the activation of the Nav1.5 and Kv2.1 channels to more depolarized voltages, and markedly shifted the steady-state inactivation of Nav1.5 currents toward more hyperpolarized potentials. Moreover, JZTX-35 can bind to a close state of Nav1.5 and Kv2.1 channels. These results indicate that JZTX-35 is a new gating modifier toxin. JZTX-35 shares high sequence similarity with Jingzhaotoxins (JZTXs) targeting Nav1.5 or Kv2.1 channels, but they showed different ion channel selectivity. Structure-function analysis in this study would provide important clues for the exploration of ion channel selectivity of JZTXs.
authors.affiliation: Key Laboratory of Psychiatric Disorders of Guangdong Province, Department of Neurobiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wei
authors.affiliation: Key Laboratory of Psychiatric Disorders of Guangdong Province, Department of Neurobiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Changxi
authors.initials: C
authors.lastname: Xu
authors.affiliation: Key Laboratory of Psychiatric Disorders of Guangdong Province, Department of Neurobiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Qiaoqi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Key Laboratory of Psychiatric Disorders of Guangdong Province, Department of Neurobiology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Lang
authors.initials: L
authors.lastname: Huang
authors.affiliation: Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China. Electronic address: liangsp@hunnu.edu.cn.
authors.forename: Songping
authors.initials: S
authors.lastname: Liang
authors.affiliation: Key Laboratory of Psychiatric Disorders of Guangdong Province, Department of Neurobiology, Southern Medical University, Guangzhou 510515, China. Electronic address: yuanch@smu.edu.cn.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Yuan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002681:China; D002851:Chromatography, High Pressure Liquid; D008969:Molecular Sequence Data; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000378:metabolism*; D009498:Neurotoxins / Q000302:isolation & purification / Q000633:toxicity*; D018408:Patch-Clamp Techniques; D051381:Rats; D017422:Sequence Analysis, DNA; D051669:Shab Potassium Channels / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013111:Spider Venoms / Q000302:isolation & purification / Q000633:toxicity*
chemical_list: C496991:Kcnb1 protein, rat; D062554:NAV1.5 Voltage-Gated Sodium Channel; D009498:Neurotoxins; C568322:Scn5a protein, rat; D051669:Shab Potassium Channels; D013111:Spider Venoms; C000599693:jingzhaotoxin-35, Chilobrachys jingzhao
keywords: Gating modifier; Kv2.1 channel; Nav1.5 channel; Spider