1. Academic Validation
  2. Molecular mechanism underlying modulation of TRPV1 heat activation by polyols

Molecular mechanism underlying modulation of TRPV1 heat activation by polyols

  • J Biol Chem. 2021 Jul;297(1):100806. doi: 10.1016/j.jbc.2021.100806.
Yingying Nie 1 Yanxin Li 1 Lei Liu 1 Shouyan Ren 2 Yuhua Tian 3 Fan Yang 4
Affiliations

Affiliations

  • 1 Department of Pharmacology, School of Pharmacy, Qingdao University Medical College, Qingdao, China.
  • 2 Department of Otorhinolaryngology, The Affiliated Hospital of Qingdao University, Qingdao, Shangdong, China.
  • 3 Department of Pharmacology, School of Pharmacy, Qingdao University Medical College, Qingdao, China. Electronic address: [email protected]
  • 4 Department of Biophysics, and Kidney Disease Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China. Electronic address: [email protected]
Abstract

Sensing noxiously high temperatures is crucial for living organisms to avoid heat-induced injury. The TRPV1 channel has long been known as a sensor for noxious heat. However, the mechanism of how this channel is activated by heat remains elusive. Here we found that a series of polyols including sucrose, sorbitol, and hyaluronan significantly elevate the heat activation threshold temperature of TRPV1. The modulatory effects of these polyols were only observed when they were perfused extracellularly. Interestingly, mutation of residues E601 and E649 in the outer pore region of TRPV1 largely abolished the effects of these polyols. We further observed that intraplantar injection of polyols into the hind paws of rats reduced their heat-induced pain response. Our observations not only suggest that the extracellular regions of TRPV1 are critical for the modulation of heat activation by polyols, but also indicate a potential role of polyols in reducing heat-induced pain sensation.

Keywords

TRPV1; heat activation; outer pore region; polyols; thermal activation threshold.

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