A centipede toxin causes rapid desensitization of nociceptor TRPV1 ion channel

Aiqin Zhu; Aerziguli Aierken; Zhihao Yao; Simon Vu; Yuhua Tian; Jie Zheng; Shilong Yang; Fan Yang

doi:10.1016/j.toxicon.2020.02.016

A centipede toxin causes rapid desensitization of nociceptor TRPV1 ion channel

Aiqin Zhu, Aerziguli Aierken, Zhihao Yao, Simon Vu, Yuhua Tian, Jie Zheng, Shilong Yang, Fan Yang

Physiology and Membrane Biology

Research output: Contribution to journal › Article

Abstract

The nociceptive transient receptor potential vanilloid 1 (TRPV1) ion channel is a polymodal receptor for multiple painful stimuli, hence actively pursued as a target for analgesic drugs. We identified a small peptide toxin RhTx2 from the Chinese red-headed centipede that strongly modulates TRPV1 activities. RhTx2, a 31-amino-acid peptide, is similar to a TRPV1-activating toxin RhTx we have previously discovered but with four extra amino acids at the N terminus. We observed that, like RhTx, RhTx2 activated TRPV1, but RhTx2 rapidly desensitized the channel upon prolonged exposure. Desensitization was achieved by reducing both the open probability and the single-channel conductance. RhTx2 is not only a tool to study the desensitization mechanism of TRPV1, but also a promising starting molecule for developing novel analgesics.

Original language	English (US)
Pages (from-to)	41-49
Number of pages	9
Journal	Toxicon
Volume	178
DOIs	https://doi.org/10.1016/j.toxicon.2020.02.016
State	Published - Apr 30 2020

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Keywords

Desensitization
Gating mechanisms
Nociception
Peptide toxins
TRPV1

ASJC Scopus subject areas

Toxicology

Cite this

Zhu, A., Aierken, A., Yao, Z., Vu, S., Tian, Y., Zheng, J., Yang, S., & Yang, F. (2020). A centipede toxin causes rapid desensitization of nociceptor TRPV1 ion channel. Toxicon, 178, 41-49. https://doi.org/10.1016/j.toxicon.2020.02.016

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title = "A centipede toxin causes rapid desensitization of nociceptor TRPV1 ion channel",

abstract = "The nociceptive transient receptor potential vanilloid 1 (TRPV1) ion channel is a polymodal receptor for multiple painful stimuli, hence actively pursued as a target for analgesic drugs. We identified a small peptide toxin RhTx2 from the Chinese red-headed centipede that strongly modulates TRPV1 activities. RhTx2, a 31-amino-acid peptide, is similar to a TRPV1-activating toxin RhTx we have previously discovered but with four extra amino acids at the N terminus. We observed that, like RhTx, RhTx2 activated TRPV1, but RhTx2 rapidly desensitized the channel upon prolonged exposure. Desensitization was achieved by reducing both the open probability and the single-channel conductance. RhTx2 is not only a tool to study the desensitization mechanism of TRPV1, but also a promising starting molecule for developing novel analgesics.",

keywords = "Desensitization, Gating mechanisms, Nociception, Peptide toxins, TRPV1",

author = "Aiqin Zhu and Aerziguli Aierken and Zhihao Yao and Simon Vu and Yuhua Tian and Jie Zheng and Shilong Yang and Fan Yang",

year = "2020",

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AU - Zhu, Aiqin

AU - Aierken, Aerziguli

AU - Yao, Zhihao

AU - Vu, Simon

AU - Tian, Yuhua

AU - Zheng, Jie

AU - Yang, Shilong

AU - Yang, Fan

PY - 2020/4/30

Y1 - 2020/4/30

N2 - The nociceptive transient receptor potential vanilloid 1 (TRPV1) ion channel is a polymodal receptor for multiple painful stimuli, hence actively pursued as a target for analgesic drugs. We identified a small peptide toxin RhTx2 from the Chinese red-headed centipede that strongly modulates TRPV1 activities. RhTx2, a 31-amino-acid peptide, is similar to a TRPV1-activating toxin RhTx we have previously discovered but with four extra amino acids at the N terminus. We observed that, like RhTx, RhTx2 activated TRPV1, but RhTx2 rapidly desensitized the channel upon prolonged exposure. Desensitization was achieved by reducing both the open probability and the single-channel conductance. RhTx2 is not only a tool to study the desensitization mechanism of TRPV1, but also a promising starting molecule for developing novel analgesics.

AB - The nociceptive transient receptor potential vanilloid 1 (TRPV1) ion channel is a polymodal receptor for multiple painful stimuli, hence actively pursued as a target for analgesic drugs. We identified a small peptide toxin RhTx2 from the Chinese red-headed centipede that strongly modulates TRPV1 activities. RhTx2, a 31-amino-acid peptide, is similar to a TRPV1-activating toxin RhTx we have previously discovered but with four extra amino acids at the N terminus. We observed that, like RhTx, RhTx2 activated TRPV1, but RhTx2 rapidly desensitized the channel upon prolonged exposure. Desensitization was achieved by reducing both the open probability and the single-channel conductance. RhTx2 is not only a tool to study the desensitization mechanism of TRPV1, but also a promising starting molecule for developing novel analgesics.

KW - Desensitization

KW - Gating mechanisms

KW - Nociception

KW - Peptide toxins

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10.1016/j.toxicon.2020.02.016