{"entity": "researcher", "timestamp": "2026-08-20T21:23:50.388Z", "family": "Chen", "given": "Zi-Wei", "initials": "ZW", "orcid": "0000-0001-8601-2210", "affiliations": ["Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/9a682f2df47e463ba58b480c71e3a457.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/9a682f2df47e463ba58b480c71e3a457"}}, "publications": [{"entity": "publication", "iuid": "07e6280efc3b4cd4b705abdc88e1bdfd", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/07e6280efc3b4cd4b705abdc88e1bdfd.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/07e6280efc3b4cd4b705abdc88e1bdfd"}}, "title": "A propofol binding site in the voltage sensor domain mediates inhibition of HCN1 channel activity.", "authors": [{"family": "Burtscher", "given": "Verena", "initials": "V", "orcid": "0000-0002-0464-0799", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/92065da7444f4b249bd33532bd77d8c5.json"}}, {"family": "Wang", "given": "Lei", "initials": "L", "orcid": "0000-0002-4572-0269", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fabada9618304484a9733869935cd597.json"}}, {"family": "Cowgill", "given": "John", "initials": "J", "orcid": "0000-0002-7968-8359", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/861488d03cd8493388b75eab8476381d.json"}}, {"family": "Chen", "given": "Zi-Wei", "initials": "ZW", "orcid": "0000-0001-8601-2210", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9a682f2df47e463ba58b480c71e3a457.json"}}, {"family": "Edge", "given": "Christopher", "initials": "C"}, {"family": "Smith", "given": "Edward", "initials": "E"}, {"family": "Chang", "given": "Yongchang", "initials": "Y", "orcid": "0009-0004-2461-6894", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0ccb59b787c44f8aa7af11f55548714b.json"}}, {"family": "Delemotte", "given": "Lucie", "initials": "L", "orcid": "0000-0002-0828-3899", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/87eaf619d7bd487ebdbe68c46b827e66.json"}}, {"family": "Evers", "given": "Alex S", "initials": "AS", "orcid": "0000-0002-0342-0575", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6d6a9cd8044c476fbc99896aae9847be.json"}}, {"family": "Chanda", "given": "Baron", "initials": "B", "orcid": "0000-0003-4954-7034", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d66119f97dd7443287276dea2fe6d844.json"}}], "type": "journal article", "published": "2025-01-03", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "11", "issue": "1", "pages": "eadr7427", "issn-l": "2375-2548"}, "abstract": "Hyperpolarization-activated and cyclic nucleotide-gated (HCN) ion channels are members of the cyclic nucleotide-binding family and are crucial for regulating cellular automaticity in many excitable cells. HCN channel activation contributes to pain perception, and propofol, a widely used anesthetic, acts as an analgesic by inhibiting the voltage-dependent activity of HCN channels. However, the molecular determinants of propofol action on HCN channels remain unknown. Here, we use a propofol-analog photoaffinity labeling reagent to identify propofol binding sites in the human HCN1 isoform. Mass spectrometry analyses combined with molecular dynamics simulations show that a binding pocket is formed by extracellularly facing residues in the S3 and S4 transmembrane segments in the resting voltage-sensor conformation. Mutations of residues within the putative binding pocket mitigate or eliminate voltage-dependent modulation of HCN1 currents by propofol. Together, these findings reveal a conformation-specific propofol binding site that underlies voltage-dependent inhibition of HCN currents and provides a framework for identifying highly specific modulators of HCN channel gating.", "doi": "10.1126/sciadv.adr7427", "pmid": "39752505", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11698089"}], "notes": [], "created": "2026-08-20T11:58:59.687Z", "modified": "2026-08-20T11:58:59.987Z"}]}