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The tarantula toxin jingzhaotoxin-XI (κ-theraphotoxin-Cj1a) regulates the activation and inactivation of the voltage-gated sodium channel Nav1.5.
Toxicon. 2014 Dec 15; 92:6-13.T

Abstract

Specific peptide toxins interact with voltage-gated sodium channels by regulating the activation or inactivation of targeted channels. However, few toxins possessing dual effects have been identified. In the present study, we showed that jingzhaotoxin-XI/κ-theraphotoxin-Cj1a (JZTX-XI), a 34-residue peptide from the venom of the Chinese spider Chilobrachys jingzhao, inhibits the sodium conductance (IC50 = 124 ± 26 nM) and slows the fast inactivation (EC50 = 1.18 ± 0.2 μM) of Nav1.5 expressed in Chinese hamster ovary (CHO-K1) cells. JZTX-XI significantly shifted the activation to more depolarized voltages and decreased the deactivation of Nav1.5 currents upon extreme depolarization, but only slightly affected voltage-dependence of steady-state inactivation. In addition, JZTX-XI caused an approximately five-fold decrease in the rate of recovery from inactivation and an approximately 1.9-fold reduction in the closed-state inactivation rate. Our data suggest that JZTX-XI integrates the functions of site 3 toxins (α-scorpion toxins) with site 4 toxins (β-scorpion and spider toxins) by targeting multiple sites on Nav1.5. The unique properties displayed by JZTX-XI in its inhibitory activity on Nav1.5 suggest that its mechanism of action is distinct from those of site 3 and site 4 toxins, making JZTX-XI a useful probe for investigating the gating mechanism of Nav1.5 and toxin-channel interactions.

Authors+Show Affiliations

College of Life Science, Hunan Normal University, Changsha 410081, China.College of Life Science, Hunan Normal University, Changsha 410081, China.College of Life Science, Hunan Normal University, Changsha 410081, China.College of Life Science, Hunan Normal University, Changsha 410081, China.College of Life Science, Hunan Normal University, Changsha 410081, China.College of Life Science, Hunan Normal University, Changsha 410081, China.College of Life Science, Hunan Normal University, Changsha 410081, China.College of Life Science, Hunan Normal University, Changsha 410081, China. Electronic address: liuzh@hunnu.edu.cn.College of Life Science, Hunan Normal University, Changsha 410081, China. Electronic address: liangsp@hunnu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25240294

Citation

Tang, Cheng, et al. "The Tarantula Toxin jingzhaotoxin-XI (κ-theraphotoxin-Cj1a) Regulates the Activation and Inactivation of the Voltage-gated Sodium Channel Nav1.5." Toxicon : Official Journal of the International Society On Toxinology, vol. 92, 2014, pp. 6-13.
Tang C, Zhou X, Huang Y, et al. The tarantula toxin jingzhaotoxin-XI (κ-theraphotoxin-Cj1a) regulates the activation and inactivation of the voltage-gated sodium channel Nav1.5. Toxicon. 2014;92:6-13.
Tang, C., Zhou, X., Huang, Y., Zhang, Y., Hu, Z., Wang, M., Chen, P., Liu, Z., & Liang, S. (2014). The tarantula toxin jingzhaotoxin-XI (κ-theraphotoxin-Cj1a) regulates the activation and inactivation of the voltage-gated sodium channel Nav1.5. Toxicon : Official Journal of the International Society On Toxinology, 92, 6-13. https://doi.org/10.1016/j.toxicon.2014.09.002
Tang C, et al. The Tarantula Toxin jingzhaotoxin-XI (κ-theraphotoxin-Cj1a) Regulates the Activation and Inactivation of the Voltage-gated Sodium Channel Nav1.5. Toxicon. 2014 Dec 15;92:6-13. PubMed PMID: 25240294.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The tarantula toxin jingzhaotoxin-XI (κ-theraphotoxin-Cj1a) regulates the activation and inactivation of the voltage-gated sodium channel Nav1.5. AU - Tang,Cheng, AU - Zhou,Xi, AU - Huang,Yin, AU - Zhang,Yunxiao, AU - Hu,Zhaotun, AU - Wang,Meichi, AU - Chen,Ping, AU - Liu,Zhonghua, AU - Liang,Songping, Y1 - 2014/09/18/ PY - 2014/07/13/received PY - 2014/09/01/revised PY - 2014/09/09/accepted PY - 2014/9/22/entrez PY - 2014/9/23/pubmed PY - 2015/7/28/medline KW - Activation KW - Gating mechanism KW - Inactivation KW - Jingzhaotoxin-XI KW - Na(v)1.5 SP - 6 EP - 13 JF - Toxicon : official journal of the International Society on Toxinology JO - Toxicon VL - 92 N2 - Specific peptide toxins interact with voltage-gated sodium channels by regulating the activation or inactivation of targeted channels. However, few toxins possessing dual effects have been identified. In the present study, we showed that jingzhaotoxin-XI/κ-theraphotoxin-Cj1a (JZTX-XI), a 34-residue peptide from the venom of the Chinese spider Chilobrachys jingzhao, inhibits the sodium conductance (IC50 = 124 ± 26 nM) and slows the fast inactivation (EC50 = 1.18 ± 0.2 μM) of Nav1.5 expressed in Chinese hamster ovary (CHO-K1) cells. JZTX-XI significantly shifted the activation to more depolarized voltages and decreased the deactivation of Nav1.5 currents upon extreme depolarization, but only slightly affected voltage-dependence of steady-state inactivation. In addition, JZTX-XI caused an approximately five-fold decrease in the rate of recovery from inactivation and an approximately 1.9-fold reduction in the closed-state inactivation rate. Our data suggest that JZTX-XI integrates the functions of site 3 toxins (α-scorpion toxins) with site 4 toxins (β-scorpion and spider toxins) by targeting multiple sites on Nav1.5. The unique properties displayed by JZTX-XI in its inhibitory activity on Nav1.5 suggest that its mechanism of action is distinct from those of site 3 and site 4 toxins, making JZTX-XI a useful probe for investigating the gating mechanism of Nav1.5 and toxin-channel interactions. SN - 1879-3150 UR - https://www.unboundmedicine.com/medline/citation/25240294/The_tarantula_toxin_jingzhaotoxin_XI__κ_theraphotoxin_Cj1a__regulates_the_activation_and_inactivation_of_the_voltage_gated_sodium_channel_Nav1_5_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-0101(14)00306-7 DB - PRIME DP - Unbound Medicine ER -