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Jingzhaotoxin-X, a gating modifier of Kv4.2 and Kv4.3 potassium channels purified from the venom of the Chinese tarantula Chilobrachys jingzhao.
J Venom Anim Toxins Incl Trop Dis. 2020 May 29; 26:e20190043.JV

Abstract

Background

The tarantula Chilobrachys jingzhao is one of the largest venomous spiders in China. In previous studies, we purified and characterized at least eight peptides from C. jingzhao venom. In this report, we describe the purification and characterization of Jingzhaotoxin-X (JZTX-X), which selectively blocks Kv4.2 and Kv4.3 potassium channels.

Methods

JZTX-X was purified using a combination of cation-exchange HPLC and reverse-phase HPLC. The amino-acid sequence was determined by automated Edman degradation and confirmed by mass spectrometry (MS). Voltage-gated ion channel currents were recorded in HEK293t cells transiently transfected with a variety of ion channel constructs. In addition, the hyperalgesic activity of JZTX-X and the toxin´s effect on motor function were assessed in mice.

Results

JZTX-X contained 31 amino acids, with six cysteine residues that formed three disulfide bonds within an inhibitory cysteine knot (ICK) topology. In whole-cell voltage-clamp experiments, JZTX-X inhibited Kv4.2 and Kv4.3 potassium channels in a concentration- and voltage-dependent manner, without affecting other ion channels (Kv1.1, 1.2, 1.3, 2.1, delayed rectifier potassium channels, high- and low-voltage-activated Ca2+ channels, and voltage-gated sodium channels Nav1.5 and 1.7). JZTX-X also shifted the voltage-dependent channel activation to more depolarized potentials, whereas extreme depolarization caused reversible toxin binding to Kv4.2 channels. JZTX-X shifted the Kv4.2 and Kv4.3 activities towards a resting state, since at the resting potential the toxin completely inhibited the channels, even in the absence of an applied physical stimulus. Intrathecal or intraplantar injection of JZTX-X caused a long-lasting decrease in the mechanical nociceptive threshold (hyperalgesia) but had no effect on motor function as assessed in the rotarod test.

Conclusions

JZTX-X selectively suppresses Kv4.2 and Kv4.3 potassium channel activity in a concentration- and voltage-dependent manner and causes long-lasting mechanical hyperalgesia.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology, School of Life Sciences, Central South University, Changsha, Hunan 410013, China.Department of Parasitology, Xiangya School of Medicine, Central South University, Changsha 410013, China.The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.Department of Biochemistry and Molecular Biology, Hunan University of Chinese Medicine, Changsha 410208, Hunan, China.The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32536941

Citation

Deng, Meichun, et al. "Jingzhaotoxin-X, a Gating Modifier of Kv4.2 and Kv4.3 Potassium Channels Purified From the Venom of the Chinese Tarantula Chilobrachys Jingzhao." The Journal of Venomous Animals and Toxins Including Tropical Diseases, vol. 26, 2020, pp. e20190043.
Deng M, Jiang L, Luo X, et al. Jingzhaotoxin-X, a gating modifier of Kv4.2 and Kv4.3 potassium channels purified from the venom of the Chinese tarantula Chilobrachys jingzhao. J Venom Anim Toxins Incl Trop Dis. 2020;26:e20190043.
Deng, M., Jiang, L., Luo, X., Tao, H., & Liang, S. (2020). Jingzhaotoxin-X, a gating modifier of Kv4.2 and Kv4.3 potassium channels purified from the venom of the Chinese tarantula Chilobrachys jingzhao. The Journal of Venomous Animals and Toxins Including Tropical Diseases, 26, e20190043. https://doi.org/10.1590/1678-9199-JVATITD-2019-0043
Deng M, et al. Jingzhaotoxin-X, a Gating Modifier of Kv4.2 and Kv4.3 Potassium Channels Purified From the Venom of the Chinese Tarantula Chilobrachys Jingzhao. J Venom Anim Toxins Incl Trop Dis. 2020 May 29;26:e20190043. PubMed PMID: 32536941.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Jingzhaotoxin-X, a gating modifier of Kv4.2 and Kv4.3 potassium channels purified from the venom of the Chinese tarantula Chilobrachys jingzhao. AU - Deng,Meichun, AU - Jiang,Liping, AU - Luo,Xuan, AU - Tao,Huai, AU - Liang,Songping, Y1 - 2020/05/29/ PY - 2020/6/16/entrez KW - Kv4 KW - Pain KW - Patch-clamp KW - Potassium channels KW - Tarantula toxin SP - e20190043 EP - e20190043 JF - The journal of venomous animals and toxins including tropical diseases JO - J Venom Anim Toxins Incl Trop Dis VL - 26 N2 - Background: The tarantula Chilobrachys jingzhao is one of the largest venomous spiders in China. In previous studies, we purified and characterized at least eight peptides from C. jingzhao venom. In this report, we describe the purification and characterization of Jingzhaotoxin-X (JZTX-X), which selectively blocks Kv4.2 and Kv4.3 potassium channels. Methods: JZTX-X was purified using a combination of cation-exchange HPLC and reverse-phase HPLC. The amino-acid sequence was determined by automated Edman degradation and confirmed by mass spectrometry (MS). Voltage-gated ion channel currents were recorded in HEK293t cells transiently transfected with a variety of ion channel constructs. In addition, the hyperalgesic activity of JZTX-X and the toxin´s effect on motor function were assessed in mice. Results: JZTX-X contained 31 amino acids, with six cysteine residues that formed three disulfide bonds within an inhibitory cysteine knot (ICK) topology. In whole-cell voltage-clamp experiments, JZTX-X inhibited Kv4.2 and Kv4.3 potassium channels in a concentration- and voltage-dependent manner, without affecting other ion channels (Kv1.1, 1.2, 1.3, 2.1, delayed rectifier potassium channels, high- and low-voltage-activated Ca2+ channels, and voltage-gated sodium channels Nav1.5 and 1.7). JZTX-X also shifted the voltage-dependent channel activation to more depolarized potentials, whereas extreme depolarization caused reversible toxin binding to Kv4.2 channels. JZTX-X shifted the Kv4.2 and Kv4.3 activities towards a resting state, since at the resting potential the toxin completely inhibited the channels, even in the absence of an applied physical stimulus. Intrathecal or intraplantar injection of JZTX-X caused a long-lasting decrease in the mechanical nociceptive threshold (hyperalgesia) but had no effect on motor function as assessed in the rotarod test. Conclusions: JZTX-X selectively suppresses Kv4.2 and Kv4.3 potassium channel activity in a concentration- and voltage-dependent manner and causes long-lasting mechanical hyperalgesia. SN - 1678-9199 UR - https://www.unboundmedicine.com/medline/citation/32536941/Jingzhaotoxin-X,_a_gating_modifier_of_Kv4.2_and_Kv4.3_potassium_channels_purified_from_the_venom_of_the_Chinese_tarantula_Chilobrachys_jingzhao DB - PRIME DP - Unbound Medicine ER -
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