RyR2 Gain-of-Function Increases Ca2+ Spark and Ca2+ Wave Activity in Vascular Smooth Muscle Cells
- 1Department of Internal Medicine and Geriatrics, University Medicine Greifswald, 17475 Greifswald, Germany
- 2DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, 17475 Greifswald, Germany
- 3Libin Cardiovascular Institute of Alberta, Department of Physiology and Pharmacology, University of Calgary, Calgary, AB T2N 4Z6, Canada
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.
Related
- RNA Splicing of the REST Gene by SRRM4 in Vascular Smooth Muscle Cells Promotes Abdominal Aortic Aneurysm Development
- Empagliflozin attenuates traumatic brain injury-induced atherosclerosis and norepinephrine-induced vascular smooth muscle cell responses
- Inhaled nanogels ameliorate vascular remodeling in pulmonary arterial hypertension via normalization of endothelia-smooth muscle cell crosstalk
- HMGA1 accelerates vascular smooth muscle cell osteogenic phenotype transdifferentiation by elevating pro-inflammatory cytokine IL-1β transcription in chronic kidney disease.
- Recognizing senescent vascular smooth muscle cells in diabetic atherosclerosis: biomarkers, transcriptomic signatures, and methodological validity
BibTeX
@article{alves2026ryr2,
title = {{RyR2 Gain-of-Function Increases Ca2+ Spark and Ca2+ Wave Activity in Vascular Smooth Muscle Cells}},
author = {Daniele Teixeira Alves and Qidi Zhai and Liming Lu and Zhugang Chu and Dmitry Tsvetkov and S. R. Wayne Chen and Maik Gollasch and Mario Kassmann},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219636},
url = {https://www.mdpi.com/1422-0067/27/21/9636},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - RyR2 Gain-of-Function Increases Ca2+ Spark and Ca2+ Wave Activity in Vascular Smooth Muscle Cells
AU - Daniele Teixeira Alves
AU - Qidi Zhai
AU - Liming Lu
AU - Zhugang Chu
AU - Dmitry Tsvetkov
AU - S. R. Wayne Chen
AU - Maik Gollasch
AU - Mario Kassmann
PY - 2026
DA - 2026/10/28
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219636
UR - https://www.mdpi.com/1422-0067/27/21/9636
AB - 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.
SN - 1422-0067
ER -