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Molecular basis for heat desensitization of TRPV1 ion channels

Author

Listed:
  • Lei Luo

    (Kunming Institute of Zoology
    University of Chinese Academy of Sciences)

  • Yunfei Wang

    (Kunming Institute of Zoology
    University of Chinese Academy of Sciences)

  • Bowen Li

    (Kunming Institute of Zoology)

  • Lizhen Xu

    (First Affiliated Hospital, Institute of Neuroscience, National Health Commission and Chinese Academy of Medical Sciences, Zhejiang University School of Medicine)

  • Peter Muiruri Kamau

    (Kunming Institute of Zoology
    University of Chinese Academy of Sciences)

  • Jie Zheng

    (University of California)

  • Fan Yang

    (First Affiliated Hospital, Institute of Neuroscience, National Health Commission and Chinese Academy of Medical Sciences, Zhejiang University School of Medicine)

  • Shilong Yang

    (Kunming Institute of Zoology)

  • Ren Lai

    (Kunming Institute of Zoology)

Abstract

The transient receptor potential vanilloid 1 (TRPV1) ion channel is a prototypical molecular sensor for noxious heat in mammals. Its role in sustained heat response remains poorly understood, because rapid heat-induced desensitization (Dh) follows tightly heat-induced activation (Ah). To understand the physiological role and structural basis of Dh, we carried out a comparative study of TRPV1 channels in mouse (mV1) and those in platypus (pV1), which naturally lacks Dh. Here we show that a temperature-sensitive interaction between the N- and C-terminal domains of mV1 but not pV1 drives a conformational rearrangement in the pore leading to Dh. We further show that knock-in mice expressing pV1 sensed heat normally but suffered scald damages in a hot environment. Our findings suggest that Dh evolved late during evolution as a protective mechanism and a delicate balance between Ah and Dh is crucial for mammals to sense and respond to noxious heat.

Suggested Citation

  • Lei Luo & Yunfei Wang & Bowen Li & Lizhen Xu & Peter Muiruri Kamau & Jie Zheng & Fan Yang & Shilong Yang & Ren Lai, 2019. "Molecular basis for heat desensitization of TRPV1 ion channels," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09965-6
    DOI: 10.1038/s41467-019-09965-6
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