{
  "abstract": "The ion pump Na + ,K + -ATPase is a critical determinant of neuronal excitability; however, its role in the etiology of diseases of the central nervous system (CNS) is largely unknown. We describe here the molecular phenotype of a Trp931Arg mutation of the Na + ,K + -ATPase catalytic α1 subunit in an infant diagnosed with therapy-resistant lethal epilepsy. In addition to the pathological CNS phenotype, we also detected renal wasting of Mg 2+ . We found that membrane expression of the mutant α1 protein was low, and ion pumping activity was lost. Arginine insertion into membrane proteins can generate water-filled pores in the plasma membrane, and our molecular dynamic (MD) simulations of the principle states of Na + ,K + -ATPase transport demonstrated massive water inflow into mutant α1 and destabilization of the ion-binding sites. MD simulations also indicated that a water pathway was created between the mutant arginine residue and the cytoplasm, and analysis of oocytes expressing mutant α1 detected a nonspecific cation current. Finally, neurons expressing mutant α1 were observed to be depolarized compared with neurons expressing wild-type protein, compatible with a lowered threshold for epileptic seizures. The results imply that Na + ,K + -ATPase should be considered a neuronal locus minoris resistentia in diseases associated with epilepsy and with loss of plasma membrane integrity.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "name": "Sofia Ygberg"
    },
    {
      "name": "Evgeny Akkuratov"
    },
    {
      "name": "Rebecca Howard"
    },
    {
      "name": "Fulya Taylan"
    },
    {
      "name": "Daniel Jans"
    },
    {
      "name": "Dhani Mahato"
    },
    {
      "name": "Adriana Katz"
    },
    {
      "name": "Paula Kinoshita"
    },
    {
      "name": "Benjamin Portal"
    },
    {
      "name": "Inger Nennesmo"
    },
    {
      "name": "Maria Lindskog"
    },
    {
      "name": "Steven J.D. Karlish"
    },
    {
      "name": "Magnus Andersson"
    },
    {
      "name": "Anna Lindstrand"
    },
    {
      "name": "Hjalmar Brismar"
    },
    {
      "name": "Anita Aperia"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/730hc7ph8w459.bib",
  "cited_by": 24,
  "doi": "10.1016/j.jbc.2021.101355",
  "fulltext_url": null,
  "id": "730hc7ph8w459",
  "issns": [
    "0021-9258",
    "1083-351X"
  ],
  "landing_url": "https://hal.science/hal-05788274v1",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "1312|Ion channel regulation and function"
    ]
  ],
  "openalex": "W3210559356",
  "pdf_url": "http://www.jbc.org/article/S0021925821011613/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-09",
  "publisher": "American Society for Biochemistry and Molecular Biology",
  "ris": "https://research.draconitic.com/paper/730hc7ph8w459.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:52Z",
      "native_id": "hal-05788274",
      "source": "hal",
      "url": "https://hal.science/hal-05788274v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Ion channel regulation and function",
      "subfield": "molecular-biology"
    }
  ],
  "title": "A missense mutation converts the Na+,K+-ATPase into an ion channel and causes therapy-resistant epilepsy",
  "title_text": "A missense mutation converts the Na+,K+-ATPase into an ion channel and causes therapy-resistant epilepsy",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:52Z",
  "url": "https://research.draconitic.com/paper/730hc7ph8w459",
  "venue": "Journal of Biological Chemistry",
  "versions": []
}