{
  "abstract": "Fibroblast-like synoviocytes (FLS) are major drivers of synovial tissue inflammation and damage during rheumatoid arthritis (RA). A hallmark of the aggressiveness of RA-FLS is their invasiveness but the molecular mechanisms that regulate this invasiveness remain poorly understood. The KCa1.1 (BK, Slo1, MaxiK, KCNMA1 ) potassium channel is a major regulator of RA-FLS pathogenicity and inhibiting KCa1.1 expression or its activity with selective blockers reduces RA-FLS invasiveness and reduces disease severity and joint damage in rat models of RA. KCa1.1 blockade induces a Ca 2+ influx in RA-FLS whose intracellular signaling results in increased cell adhesion to the extracellular matrix and thus a reduction in cell migration. However, the identity of the Ca 2+ -permeable channel responsible for the Ca 2+ influx has remained elusive. Here, we demonstrate the co-expression of KCa1.1 with the L-type voltage-gated CaV1.2 channels at the plasma membrane of primary human and rat FLS. Selective blocking of the CaV1.2 channel blunts the Ca 2+ influx induced by KCa1.1 blockade and abrogates the effects of KCa1.1 blockade on RA-FLS invasiveness, migration, cell shape, and podoplanin expression. Whereas KCa1.1 blockers reduce disease severity in rat models of RA, treating rats with the collagen-induced arthritis model of RA with both blockers of KCa1.1 and CaV1.2 eliminates the therapeutic benefits of treatment with KCa1.1 blockers alone. Together, these data demonstrate a physical and functional coupling of KCa1.1 and CaV1.2 channels in FLS during RA and its rat model that regulate the invasive phenotype of the FLS through modulation of intracellular Ca 2+ homeostasis. Significance Statement This study identifies the expression of CaV1.2 Ca 2+ channels in primary fibroblast-like synoviocytes isolated from the joints of patients with rheumatoid arthritis. CaV1.2 channels are functionally coupled with KCa1.1 K + channels to regulate the highly invasive phenotype of these synoviocytes, as blocking KCa1.1 induces a Ca 2+ influx through opening of CaV1.2 that increases the adhesion of fibroblast-like synoviocytes and inhibits their migration. Conversely, blocking CaV1.2 negates the beneficial effects of KCa1.1 on the synoviocytes in vitro and abrogates the therapeutics effects of a KCa1.1 blocker in reducing clinical signs of collagen-induced arthritis.",
  "abstract_shown": true,
  "affiliations": [
    "Baylor College of Medicine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "name": "M. R. Tanner"
    },
    {
      "name": "R. N. Elston"
    },
    {
      "name": "M. J. Brandt"
    },
    {
      "name": "B. A. Morse"
    },
    {
      "name": "L. Sun"
    },
    {
      "name": "S. Zou"
    },
    {
      "name": "J. M. Hyser"
    },
    {
      "name": "F. T. Horrigan"
    },
    {
      "name": "T. Laragione"
    },
    {
      "name": "P. S. Gulko"
    },
    {
      "affs": [
        0
      ],
      "name": "C. Beeton"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/56ghcb5dhryz9.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.12.758622",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.12.758622v1.full",
  "id": "56ghcb5dhryz9",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.12.758622v1",
  "language": null,
  "licence": "PDM-1.0",
  "licence_label": "Public domain",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/publicdomain/mark/1.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cell biology"
    ],
    [
      "openalex",
      "2745|Rheumatoid Arthritis Research and Therapies"
    ]
  ],
  "openalex": "W7221805904",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.12.758622v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-12",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/56ghcb5dhryz9.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:46Z",
      "native_id": "10.64898/2026.10.12.758622",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.12.758622v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "The L-type voltage-gated Ca2+ channel CaV1.2 regulates fibroblast-like synoviocytes invasiveness during rheumatoid arthritis",
  "title_text": "The L-type voltage-gated Ca2+ channel CaV1.2 regulates fibroblast-like synoviocytes invasiveness during rheumatoid arthritis",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:46Z",
  "url": "https://research.draconitic.com/paper/56ghcb5dhryz9",
  "venue": "bioRxiv",
  "versions": []
}