{
  "abstract": "Ca2+ sparks in vascular smooth muscle cells (VSMCs) regulate vascular function, and their dysregulation with ageing may contribute to vascular disease. These localized Ca2+ signals originate from ryanodine receptors (RyRs) and can initiate propagating Ca2+ waves that modulate vascular tone. However, it is still unclear which RyR isoform (RyR1, RyR2, or RyR3) primarily drives these Ca2+ signals in arterial VSMCs, as all three are present. The RyR2 contribution to vascular Ca2+ signaling was analyzed using Ca2+ sparks and waves in arterial VSMCs isolated from mice carrying the RyR2R4496C mutation. Intracellular Ca2+ signals were recorded using a fluorescent Ca2+ indicator in VSMCs from both young and older mice. Caffeine-evoked Ca2+ responses and contractions were measured to assess RyR-mediated SR Ca2+ release and vascular reactivity. VSMCs from young RyR2R4496C mice exhibited a significantly higher frequency of Ca2+ sparks and a greater percentage of cells displaying Ca2+ sparks and propagating Ca2+ waves compared with controls. The RyR2R4496C mutation enhanced RyR2 sensitivity to caffeine, resulting in larger increases in intracellular [Ca2+]i and arterial contractions in older mice. These findings demonstrate that RyR2 gain-of-function increases Ca2+ spark and Ca2+ wave activity in VSMCs, supporting a role for RyR2 in the regulation of local and propagating Ca2+ signals. Dysregulated RyR2 activity may therefore contribute to altered vascular Ca2+ signaling and could represent a potential mechanistic link to vascular dysfunction associated with ageing and metabolic stress.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Internal Medicine and Geriatrics, University Medicine Greifswald, 17475 Greifswald, Germany",
    "DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, 17475 Greifswald, Germany",
    "Libin Cardiovascular Institute of Alberta, Department of Physiology and Pharmacology, University of Calgary, Calgary, AB T2N 4Z6, Canada"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Daniele Teixeira Alves"
    },
    {
      "affs": [
        0
      ],
      "name": "Qidi Zhai"
    },
    {
      "affs": [
        0
      ],
      "name": "Liming Lu"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhugang Chu",
      "orcid": "0009-0000-9084-8942"
    },
    {
      "affs": [
        0
      ],
      "name": "Dmitry Tsvetkov"
    },
    {
      "affs": [
        2
      ],
      "name": "S. R. Wayne Chen",
      "orcid": "0000-0001-5808-0304"
    },
    {
      "affs": [
        0
      ],
      "name": "Maik Gollasch",
      "orcid": "0000-0003-2797-1934"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Mario Kassmann",
      "orcid": "0000-0002-4785-6530"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2a55dmn9v6q9f.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27219636",
  "fulltext_url": null,
  "id": "2a55dmn9v6q9f",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/9636",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2705|Cardiac electrophysiology and arrhythmias"
    ]
  ],
  "openalex": "W7224084893",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-28",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/2a55dmn9v6q9f.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:57Z",
      "native_id": "10.3390/ijms27219636",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/9636"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2705|Cardiac electrophysiology and arrhythmias",
      "subfield": "cardiovascular"
    }
  ],
  "title": "RyR2 Gain-of-Function Increases Ca2+ Spark and Ca2+ Wave Activity in Vascular Smooth Muscle Cells",
  "title_text": "RyR2 Gain-of-Function Increases Ca2+ Spark and Ca2+ Wave Activity in Vascular Smooth Muscle Cells",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:57Z",
  "url": "https://research.draconitic.com/paper/2a55dmn9v6q9f",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}