{"entity": "researcher", "timestamp": "2026-03-09T08:50:41.151Z", "family": "Liang", "given": "Qiansheng", "initials": "Q", "orcid": "0009-0009-0856-1957", "affiliations": ["Department of Neuroscience and Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA 19107."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/ee4ab9ab889143cab8c24c31605476bf.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/ee4ab9ab889143cab8c24c31605476bf"}}, "publications": [{"entity": "publication", "iuid": "a8a78e40c92a48dca0e2226b3627c2ae", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/a8a78e40c92a48dca0e2226b3627c2ae.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/a8a78e40c92a48dca0e2226b3627c2ae"}}, "title": "A structurally precise mechanism links an epilepsy-associated KCNC2 potassium channel mutation to interneuron dysfunction.", "authors": [{"family": "Clatot", "given": "Jerome", "initials": "J"}, {"family": "Currin", "given": "Christopher B", "initials": "CB"}, {"family": "Liang", "given": "Qiansheng", "initials": "Q", "orcid": "0009-0009-0856-1957", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ee4ab9ab889143cab8c24c31605476bf.json"}}, {"family": "Pipatpolkai", "given": "Tanadet", "initials": "T"}, {"family": "Massey", "given": "Shavonne L", "initials": "SL"}, {"family": "Helbig", "given": "Ingo", "initials": "I"}, {"family": "Delemotte", "given": "Lucie", "initials": "L", "orcid": "0000-0002-0828-3899", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/87eaf619d7bd487ebdbe68c46b827e66.json"}}, {"family": "Vogels", "given": "Tim P", "initials": "TP", "orcid": "0000-0003-3295-6181", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3adfacc0cac346d082c96055f3c87fe3.json"}}, {"family": "Covarrubias", "given": "Manuel", "initials": "M"}, {"family": "Goldberg", "given": "Ethan M", "initials": "EM", "orcid": "0000-0002-7404-735X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/36ba7e3b0df74614ba91bac736cbd20e.json"}}], "type": "journal article", "published": "2024-01-16", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "volume": "121", "issue": "3", "pages": "e2307776121", "issn-l": "0027-8424"}, "abstract": "De novo heterozygous variants in KCNC2 encoding the voltage-gated potassium (K+) channel subunit Kv3.2 are a recently described cause of developmental and epileptic encephalopathy (DEE). A de novo variant in KCNC2 c.374G > A (p.Cys125Tyr) was identified via exome sequencing in a patient with DEE. Relative to wild-type Kv3.2, Kv3.2-p.Cys125Tyr induces K+ currents exhibiting a large hyperpolarizing shift in the voltage dependence of activation, accelerated activation, and delayed deactivation consistent with a relative stabilization of the open conformation, along with increased current density. Leveraging the cryogenic electron microscopy (cryo-EM) structure of Kv3.1, molecular dynamic simulations suggest that a strong \u03c0-\u03c0 stacking interaction between the variant Tyr125 and Tyr156 in the \u03b1-6 helix of the T1 domain promotes a relative stabilization of the open conformation of the channel, which underlies the observed gain of function. A multicompartment computational model of a Kv3-expressing parvalbumin-positive cerebral cortex fast-spiking \u03b3-aminobutyric acidergic (GABAergic) interneuron (PV-IN) demonstrates how the Kv3.2-Cys125Tyr variant impairs neuronal excitability and dysregulates inhibition in cerebral cortex circuits to explain the resulting epilepsy.", "doi": "10.1073/pnas.2307776121", "pmid": "38194456", "labels": {"Lucie Delemotte": null, "SciLifeLab Fellow": null}, "xrefs": [{"db": "pmc", "key": "PMC10801864"}], "notes": [], "created": "2024-11-26T05:26:28.255Z", "modified": "2024-11-26T05:26:28.404Z"}]}