ArticlePhilosophical transactions of the Royal Society of London. Series B, Biological sciences2022
Three-dimensional visualization of the cardiac ryanodine receptor clusters and the molecular-scale fraying of dyads.
Article in Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- Structural Integrity of RyR2 Clusters Controls Cardiac Calcium Leak.bioRxiv : the preprint server for biology · 2025Article
- Expansion microscopy reveals nano-scale insights into the human neuromuscular junction.Cell reports methods · 2025Article
- Functional analysis of JPH2-knockout cardiomyocytes identifies ECCD as a novel indicator in a human cardiac modelJPH2.Stem cell research & therapy · 2025Article
- Structural integrity of RyR2 clusters controls cardiac calcium leak.Frontiers in physiology · 2025Article
- Nanoscale organization of cardiac calcium channels is dependent on thyroid hormone status.American journal of physiology. Heart and circulatory physiology · 2024Article
- Clustering properties of the cardiac ryanodine receptor in health and heart failure.Journal of molecular and cellular cardiology · 2023Review
- The role of Zn2+ in shaping intracellular Ca2+ dynamics in the heart.The Journal of general physiology · 2023Review
- Correlative super-resolution analysis of cardiac calcium sparks and their molecular origins in health and disease.Open biology · 2023Article
- Expansion microscopy reveals subdomains inLife science alliance · 2023Article
- Increased Mitochondrial Calcium Fluxes in Hypertrophic Right Ventricular Cardiomyocytes from a Rat Model of Pulmonary Artery Hypertension.Life (Basel, Switzerland) · 2023Article
- Three-dimensional visualization of the cardiac ryanodine receptor clusters and the molecular-scale fraying of dyads.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022Article
- New revelations on the interplay between cardiomyocyte architecture and cardiomyocyte function in growth, health, and disease: a brief introduction.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Clusters of ryanodine receptor calcium channels (RyRs) form the primary molecular machinery of intracellular calcium signalling in cardiomyocytes. While a range of optical super-resolution microscopy techniques have revealed the nanoscale structure of these clusters, the three-dimensional (3D) nanoscale topologies of the clusters have remained mostly unresolved. In this paper, we demonstrate the exploitation of molecular-scale resolution in enhanced expansion microscopy (EExM) along with various 2D and 3D visualization strategies to observe the topological complexities, geometries and molecular sub-domains within the RyR clusters. Notably, we observed sub-domains containing RyR-binding protein junctophilin-2 (JPH2) occupying the central regions of RyR clusters in the deeper interior of the myocytes (including dyads), while the poles were typically devoid of JPH2, lending to a looser RyR arrangement. By contrast, peripheral RyR clusters exhibited variable co-clustering patterns and ratios between RyR and JPH2. EExM images of dyadic RyR clusters in right ventricular (RV) myocytes isolated from rats with monocrotaline-induced RV failure revealed hallmarks of RyR cluster fragmentation accompanied by breaches in the JPH2 sub-domains. Frayed RyR patterns observed adjacent to these constitute new evidence that the destabilization of the RyR arrays inside the JPH2 sub-domains may seed the primordial foci of dyad remodelling observed in heart failure. This article is part of the theme issue 'The cardiomyocyte: new revelations on the interplay between architecture and function in growth, health, and disease'.
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