Molecular basis for heat desensitization of TRPV1 ion channels

Lei Luo, Yunfei Wang, Bowen Li, Lizhen Xu, Peter Muiruri Kamau, Jie Zheng, Fan Yang, Shilong Yang, Ren Lai

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6 Scopus citations

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.

Original languageEnglish (US)
Article number2134
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Luo, L., Wang, Y., Li, B., Xu, L., Kamau, P. M., Zheng, J., Yang, F., Yang, S., & Lai, R. (2019). Molecular basis for heat desensitization of TRPV1 ion channels. Nature communications, 10(1), [2134]. https://doi.org/10.1038/s41467-019-09965-6