{"entity": "researcher", "timestamp": "2026-08-18T15:19:02.601Z", "family": "Taglialatela", "given": "Maurizio", "initials": "M", "orcid": "0000-0002-8202-0560", "affiliations": ["Department of Neuroscience, University of Naples \"Federico II\", Naples, Italy. maurizio.taglialatela@unina.it."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/e63120f3ede941f28a57347a9d37375d.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/e63120f3ede941f28a57347a9d37375d"}}, "publications": [{"entity": "publication", "iuid": "40ba10959068438883c1c5fa74267dfd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/40ba10959068438883c1c5fa74267dfd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/40ba10959068438883c1c5fa74267dfd"}}, "title": "Two-step voltage-sensor activation of the human KV7.4 channel and effect of a deafness-associated mutation.", "authors": [{"family": "Nappi", "given": "Mario", "initials": "M", "orcid": "0000-0002-1243-0935", "researcher": {"href": "https://publications.scilifelab.se/researcher/c10c80f3956c4f0eb0ec6527924c9e39.json"}}, {"family": "Frampton", "given": "Damon J A", "initials": "DJA"}, {"family": "Kusay", "given": "Ali S", "initials": "AS"}, {"family": "Wang", "given": "Kaiqian", "initials": "K", "orcid": "0000-0002-6315-8732", "researcher": {"href": "https://publications.scilifelab.se/researcher/ab60287e78114936a54d018ce6fc7d28.json"}}, {"family": "Yasarbas", "given": "S Suheda", "initials": "SS", "orcid": "0009-0002-8528-2539", "researcher": {"href": "https://publications.scilifelab.se/researcher/2b15e89897e04bedaf5b070a03959a9f.json"}}, {"family": "Pozzi", "given": "Serena", "initials": "S"}, {"family": "Miceli", "given": "Francesco", "initials": "F"}, {"family": "Liin", "given": "Sara I", "initials": "SI", "orcid": "0000-0001-8493-0114", "researcher": {"href": "https://publications.scilifelab.se/researcher/e82a591108f24dcabf50779d88fc8844.json"}}, {"family": "Taglialatela", "given": "Maurizio", "initials": "M", "orcid": "0000-0002-8202-0560", "researcher": {"href": "https://publications.scilifelab.se/researcher/e63120f3ede941f28a57347a9d37375d.json"}}, {"family": "Pantazis", "given": "Antonios", "initials": "A", "orcid": "0000-0002-6467-1327", "researcher": {"href": "https://publications.scilifelab.se/researcher/810aaa85bf734f03a9e25e0651b45c19.json"}}], "type": "journal article", "published": "2026-02-05", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "17", "issue": "1", "issn-l": "2041-1723"}, "abstract": "KCNQ4-encoded KV7.4 voltage-gated potassium channels are expressed in hair-cells of the inner ear. Loss-of-function variants in KCNQ4 cause non-syndromic progressive hearing loss (DFNA2). KV7.4 pore opening requires voltage-dependent conformational changes (activation) of the voltage-sensor domains (VSDs); however, how fast charge displacement during VSD activation is coupled to slow channel opening is currently unclear. Here, we optically tracked KV7.4 VSD activation with voltage-clamp fluorometry, leveraging two fluorophores and pulsed excitation, and found that VSD activation comprises several voltage-dependent transitions, some with kinetics and voltage-dependence matching those of channel opening and closing. The DFNA2-causing R216H mutation impairs VSD movement and channel opening by destabilizing the active VSD configuration, a result confirmed by molecular dynamics simulations. We propose that the KV7.4 VSD activates in two steps: a fast movement representing a first transition to an intermediate activation state, followed by slower component(s) that fully activate the VSD and drive channel opening.", "doi": "10.1038/s41467-026-69249-8", "pmid": "41639121", "labels": {"Clinical Genomics": "Service", "Clinical Genomics Link\u00f6ping": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12982505"}, {"db": "pii", "key": "10.1038/s41467-026-69249-8"}], "notes": [], "created": "2026-08-18T07:32:13.346Z", "modified": "2026-08-18T07:32:13.949Z"}]}