{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Physiology and Membrane Biology, University of California Davis, School of Medicine, Davis, CA 95616.",
    "Department of Physiology, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea.",
    "Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao 266071, China.",
    "Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology, Daegu 42988, Republic of Korea."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Bo Hyun Lee",
      "orcid": "0000-0003-2652-8797"
    },
    {
      "affs": [
        0
      ],
      "name": "Shisheng Li",
      "orcid": "0000-0002-8340-1373"
    },
    {
      "affs": [
        0
      ],
      "name": "Simon Vu",
      "orcid": "0000-0002-1529-8220"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhihao Yao"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Yuhua Tian"
    },
    {
      "affs": [
        0
      ],
      "name": "Vladimir Yarov-Yarovoy",
      "orcid": "0000-0002-2325-4834"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Jie Zheng",
      "orcid": "0000-0002-4161-627X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1kpejsbk033jr.bib",
  "cited_by": 0,
  "doi": "10.1073/pnas.2614335123",
  "fulltext_url": "https://europepmc.org/articles/PMC13684282",
  "id": "1kpejsbk033jr",
  "issns": [
    "0027-8424",
    "1091-6490"
  ],
  "landing_url": "https://europepmc.org/article/MED/42879484",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2809|Ion Channels and Receptors"
    ]
  ],
  "openalex": "W7222029133",
  "pdf_url": "https://europepmc.org/articles/PMC13684282?pdf=render",
  "pmcid": "PMC13684282",
  "pmid": "42879484",
  "published": "2026-10-15",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/1kpejsbk033jr.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:46Z",
      "native_id": "MED:42879484",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42879484"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2809|Ion Channels and Receptors",
      "subfield": "neuroscience"
    }
  ],
  "title": "Distinct functional open states of the polymodal nociceptor TRPV1.",
  "title_text": "Distinct functional open states of the polymodal nociceptor TRPV1.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:46Z",
  "url": "https://research.draconitic.com/paper/1kpejsbk033jr",
  "venue": "Proceedings of the National Academy of Sciences of the United States of America",
  "versions": []
}