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Peer-reviewedCC BYProceedings of the National Academy of Sciences of the United States of America

Distinct functional open states of the polymodal nociceptor TRPV1.

  • Bo Hyun Lee1,2
  • Shisheng Li1
  • Simon Vu1
  • Zhihao Yao1
  • Yuhua Tian1,3
  • Vladimir Yarov-Yarovoy1
  • Jie Zheng1,4
4 affiliations
  1. 1Department of Physiology and Membrane Biology, University of California Davis, School of Medicine, Davis, CA 95616.
  2. 2Department of Physiology, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea.
  3. 3Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao 266071, China.
  4. 4Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology, Daegu 42988, Republic of Korea.
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Abstract

The polymodal nociceptor TRPV1 integrates diverse physical and chemical stimuli, yet whether these inputs drive a common activated state remains unresolved. Here, we show that TRPV1 activators stabilize functionally distinct open states that yield discrete single-channel conductance levels. These functional states appear to arise from distinct open-pore conformations, as evidenced by anomalous mole fraction effect measurements. Structurally, stimulus-specific changes in pore conformation were directly observed using site-directed fluorescence recordings, consistent with Rosetta-guided structural models. Notably, coactivation by two stimuli markedly slows channel opening rather than producing synergistic acceleration, suggesting potential conformational incompatibility across subunits. Together, these findings define TRPV1 gating as a stimulus-partitioned, multistate process and highlight opportunities for selective modulation of TRPV1 in pain management.

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Cite

BibTeXRIS
BibTeX
@article{lee2026distinct,
  title = {{Distinct functional open states of the polymodal nociceptor TRPV1.}},
  author = {Bo Hyun Lee and Shisheng Li and Simon Vu and Zhihao Yao and Yuhua Tian and Vladimir Yarov-Yarovoy and Jie Zheng},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  year = {2026},
  month = oct,
  doi = {10.1073/pnas.2614335123},
  url = {https://europepmc.org/article/MED/42879484},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Distinct functional open states of the polymodal nociceptor TRPV1.
AU  - Bo Hyun Lee
AU  - Shisheng Li
AU  - Simon Vu
AU  - Zhihao Yao
AU  - Yuhua Tian
AU  - Vladimir Yarov-Yarovoy
AU  - Jie Zheng
PY  - 2026
DA  - 2026/10/15
JO  - Proceedings of the National Academy of Sciences of the United States of America
DO  - 10.1073/pnas.2614335123
UR  - https://europepmc.org/article/MED/42879484
AB  - The polymodal nociceptor TRPV1 integrates diverse physical and chemical stimuli, yet whether these inputs drive a common activated state remains unresolved. Here, we show that TRPV1 activators stabilize functionally distinct open states that yield discrete single-channel conductance levels. These functional states appear to arise from distinct open-pore conformations, as evidenced by anomalous mole fraction effect measurements. Structurally, stimulus-specific changes in pore conformation were directly observed using site-directed fluorescence recordings, consistent with Rosetta-guided structural models. Notably, coactivation by two stimuli markedly slows channel opening rather than producing synergistic acceleration, suggesting potential conformational incompatibility across subunits. Together, these findings define TRPV1 gating as a stimulus-partitioned, multistate process and highlight opportunities for selective modulation of TRPV1 in pain management.
SN  - 0027-8424
SN  - 1091-6490
ER  -