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Scientists Reveal Molecular Basis for Heat Desensitization of TRPV1 Ion Channels

May 14, 2019

TRPV1 is an important temperature sensing element in mammals, which can be activated by high temperatures above 40°C. However, its role in sustained heat response remains poorly understood since a rapid heat-induced desensitization (Dh) process follows a tightly heat-induced activation (Ah) phase, and its function in mammalian biological activities remain elusive.  

Recently, scientists from Kunming Institute of Zoology (KIZ) of Chinese Academy of Sciences, Zhejiang University and the University of California, Davis, reported the molecular basis for Dh of mammalian TRPV1, and showed the biological significance of Dh by using transgenic mice. The study was published in Nature Communications. 

A TRPV1 that undergoes Ah without Dh was required to be used as a template for the research at both the molecular and animal levels. Through species evolution analysis and functional research, scientists obtained the platypus TRPV1 (pV1) which undergoes Ah without Dh. 

By means of chimera construction, fluorescent unnatural amino acid labeling, fluorescence resonance energy transfer and allosteric conformation simulation, they found that the Dh of TRPV1 depends on the interaction between the N- terminal and C- terminal, thus driving the allosteric and closing of the pore region, whereas pV1 does not undergo Dh. 

To explore the biological significance of TRPV1 Dh, scientists constructed the platypus trpv1 (p-trpv1) transgenic knock-in mice. The results showed that compared to the p-trpv1 mice, wild-type mice are more tolerant to sustained heat stimulation whereas the p-trpv1 mice prefer to keep walking to avoid the stimulation of hot plates.  

This study revealed the molecular basis for Dh of TRPV1 channels and its biological significance in mammalian evolution. It also showed that TRPV1 Dh is a very important high-temperature protection mechanism for higher mammals. 

As one of the most primitive mammals, the platypus has yet to evolve a high temperature-mediated "activation-desensitization" equilibrium mechanism. Therefore, the platypus is extremely sensitive to a temperature higher than 25 °C and it is difficult for it to adapt to extreme terrestrial living conditions.  

 

Molecular basis for heat desensitization of TRPV1 channels and its biological significance in mammalian tolerance to heat. (Image by LAI Ren's Group) 

Contact

HE Linxi

Kunming Institute of Zoology

E-mail:

Molecular basis for heat desensitization of TRPV1 ion channels

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