{
  "abstract": "The M-current, generated by voltage gated KV7.2/7.3 channels, sets the threshold for neuronal action potential and acts as a key brake on repetitive firing. The M-current is tightly regulated by signaling molecules, such as calmodulin and phosphatidylinositol-4,5-bisphosphate (PIP2). Here, we show that coexpression of the ubiquitous subunit dimer of heterotrimeric G-proteins, G{beta}{gamma}, with KV7.2/7.3 in Xenopus laevis oocytes doubles maximal M-current. This regulation requires free, prenylated, membrane-associated G{beta}{gamma} and operates via two distinct mechanisms: 1) increasing plasma membrane (PM) channel density and 2) stabilizing KV7.2/7.3-PIP2 coupling. Conversely, G{beta}{gamma} scavengers reduce basal KV7.2/7.3 current and weaken PIP2 coupling. Proximity ligation assays confirm colocalization of G{beta}{gamma} and KV7.2/7.3 in the PM. Peptide array and AlphaFold modeling identify putative interaction sites on the channel cytoplasmic domain. Finally, the disease-causing G{beta}1 variant I80N abolished G{beta}{gamma}-induced M-current potentiation. Together, these findings establish G{beta}{gamma} as a significant physiological regulator and potential site of vulnerability in neuronal M-current function.",
  "abstract_shown": true,
  "affiliations": [
    "Tel Aviv University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "B. Shalomov"
    },
    {
      "name": "I. Papa-Dmitrieva"
    },
    {
      "name": "T. Keren Raifman"
    },
    {
      "name": "S. Weiss"
    },
    {
      "name": "F. De Martino"
    },
    {
      "name": "A. Gali-Sayag"
    },
    {
      "name": "J. A. Hirsch"
    },
    {
      "name": "M. Taglialatela"
    },
    {
      "name": "V. Barrese"
    },
    {
      "name": "K. Zuehlke"
    },
    {
      "name": "E. Klussmann"
    },
    {
      "name": "I. Greenwood"
    },
    {
      "name": "I. Lotan"
    },
    {
      "affs": [
        0
      ],
      "name": "N. Dascal"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1r9k9q5wfbfxm.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.15.751787",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.15.751787v1.full",
  "id": "1r9k9q5wfbfxm",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.15.751787v1",
  "language": null,
  "licence": "CC-BY-ND",
  "licence_label": "CC BY-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "physiology"
    ],
    [
      "openalex",
      "1312|Ion channel regulation and function"
    ]
  ],
  "openalex": "W7213942871",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.15.751787v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-15",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/1r9k9q5wfbfxm.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:33Z",
      "native_id": "10.64898/2026.09.15.751787",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.15.751787v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:physiology",
      "subfield": "physiology"
    }
  ],
  "title": "Gβγ dually regulates the M current via increased channel surface expression and PIP2 sensitivity",
  "title_text": "Gβγ dually regulates the M current via increased channel surface expression and PIP2 sensitivity",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:33Z",
  "url": "https://research.draconitic.com/paper/1r9k9q5wfbfxm",
  "venue": "bioRxiv",
  "versions": []
}