{"entity": "publication", "iuid": "12cc13dbbf214df3bb83a21406942480", "timestamp": "2026-08-25T09:34:38.674Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/12cc13dbbf214df3bb83a21406942480.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/12cc13dbbf214df3bb83a21406942480"}}, "title": "A rich conformational palette underlies human CaV2.1-channel availability.", "authors": [{"family": "Wang", "given": "Kaiqian", "initials": "K"}, {"family": "Nilsson", "given": "Michelle", "initials": "M", "orcid": "0000-0002-0891-7732", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/87d7e1b9d905491bb4034354fd1920ed.json"}}, {"family": "Angelini", "given": "Marina", "initials": "M", "orcid": "0000-0003-4621-3784", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/95797371087645f8b0e4d0ee78dd6c36.json"}}, {"family": "Olcese", "given": "Riccardo", "initials": "R", "orcid": "0000-0003-4225-9814", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4336bc86b7ac4691a9171b71df35747f.json"}}, {"family": "Elinder", "given": "Fredrik", "initials": "F", "orcid": "0000-0001-9125-5583", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6af26d4c0637492696fb91a3417fe902.json"}}, {"family": "Pantazis", "given": "Antonios", "initials": "A", "orcid": "0000-0002-6467-1327", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b21a9988bae64c009d8e96a01623ec15.json"}}], "type": "journal article", "published": "2025-04-23", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "16", "issue": "1", "pages": "3815", "issn-l": "2041-1723"}, "abstract": "Depolarization-evoked opening of CaV2.1 (P/Q-type) Ca2+-channels triggers neurotransmitter release, while voltage-dependent inactivation (VDI) limits channel availability to open, contributing to synaptic plasticity. The mechanism of CaV2.1 response to voltage is unclear. Using voltage-clamp fluorometry and kinetic modeling, we optically track and physically characterize the structural dynamics of the four CaV2.1 voltage-sensor domains (VSDs). The VSDs are differentially sensitive to voltage changes, both brief and long-lived. VSD-I seems to directly drive opening and convert between two modes of function, associated with VDI. VSD-II is apparently voltage-insensitive. VSD-III and VSD-IV sense more negative voltages and undergo voltage-dependent conversion uncorrelated with VDI. Auxiliary \u03b2-subunits regulate VSD-I-to-pore coupling and VSD conversion kinetics. Hence, the central role of CaV2.1 channels in synaptic release, and their contribution to plasticity, memory formation and learning, can arise from the voltage-dependent conformational changes of VSD-I.", "doi": "10.1038/s41467-025-58884-2", "pmid": "40268901", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12019389"}, {"db": "pii", "key": "10.1038/s41467-025-58884-2"}], "notes": [], "created": "2026-08-21T11:50:07.081Z", "modified": "2026-08-21T11:50:07.296Z"}