ArticleCirculation research2021
Beat-by-Beat Cardiomyocyte T-Tubule Deformation Drives Tubular Content Exchange.
Article in Circulation research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 39 citations in OpenAlex.
- Constructal law prediction of cardiomyocyte membrane architecture in physiology and disease.Bio Systems · 2026Article
- Cardiac myofibril networks induce shear stress.NPJ systems biology and applications · 2026Article
- Dysferlin stabilizes membrane nanodomains of cardiomyocytes after myocardial infarction.Scientific reports · 2026Article
- Modeling autoregulation of cardiac excitation-Ca-contraction and arrhythmogenic activities in response to mechanical load changes.iScience · 2025Article
- Molecular mechanisms underlying NLRP3 inflammasome activation and IL-1β production in air pollution fine particulate matter (PMEnvironmental pollution (Barking, Essex : 1987) · 2024Article
- Caveola mechanotransduction reinforces the cortical cytoskeleton to promote epithelial resilience.Molecular biology of the cell · 2023Article
- The heterocellular heart: identities, interactions, and implications for cardiology.Basic research in cardiology · 2023Review
- Mechanisms of spontaneous CaThe Journal of physiology · 2023Article
- Mechanisms of spontaneous CaThe Journal of physiology · 2023Article
- Endoplasmic Reticulum-Plasma Membrane Junctions as Sites of Depolarization-Induced CaAnnual review of physiology · 2023Review
- Electron microscopy of cardiac 3D nanodynamics: form, function, future.Nature reviews. Cardiology · 2022Review
- Piezo1 is the cardiac mechanosensor that initiates the cardiomyocyte hypertrophic response to pressure overload in adult mice.Nature cardiovascular research · 2022Article
- Region-specific distribution of transversal-axial tubule system organization underlies heterogeneity of calcium dynamics in the right atrium.American journal of physiology. Heart and circulatory physiology · 2022Article
- Review
- Nano-scale morphology of cardiomyocyte t-tubule/sarcoplasmic reticulum junctions revealed by ultra-rapid high-pressure freezing and electron tomography.Journal of molecular and cellular cardiology · 2021Article
- Nanoscale Organization, Regulation, and Dynamic Reorganization of Cardiac Calcium Channels.Frontiers in physiology · 2021Review
- Novel Optics-Based Approaches for Cardiac Electrophysiology: A Review.Frontiers in physiology · 2021Review
- The Physiology and Pathophysiology of T-Tubules in the Heart.Frontiers in physiology · 2021Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
rationaleThe sarcolemma of cardiomyocytes contains many proteins that are essential for electromechanical function in general, and excitation-contraction coupling in particular. The distribution of these proteins is nonuniform between the bulk sarcolemmal surface and membrane invaginations known as transverse tubules (TT). TT form an intricate network of fluid-filled conduits that support electromechanical synchronicity within cardiomyocytes. Although continuous with the extracellular space, the narrow lumen and the tortuous structure of TT can form domains of restricted diffusion. As a result of unequal ion fluxes across cell surface and TT membranes, limited diffusion may generate ion gradients within TT, especially deep within the TT network and at high pacing rates.
objectiveWe postulate that there may be an advective component to TT content exchange, wherein cyclic deformation of TT during diastolic stretch and systolic shortening serves to mix TT luminal content and assists equilibration with bulk extracellular fluid. METHODS AND
resultsUsing electron tomography, we explore the 3-dimensional nanostructure of TT in rabbit ventricular myocytes, preserved at different stages of the dynamic cycle of cell contraction and relaxation. We show that cellular deformation affects TT shape in a sarcomere length-dependent manner and on a beat-by-beat time-scale. Using fluorescence recovery after photobleaching microscopy, we show that apparent speed of diffusion is affected by the mechanical state of cardiomyocytes, and that cyclic contractile activity of cardiomyocytes accelerates TT diffusion dynamics.
conclusionsOur data confirm the existence of an advective component to TT content exchange. This points toward a novel mechanism of cardiac autoregulation, whereby the previously implied increased propensity for TT luminal concentration imbalances at high electrical stimulation rates would be countered by elevated advection-assisted diffusion at high mechanical beating rates. The relevance of this mechanism in health and during pathological remodeling (eg, cardiac hypertrophy or failure) forms an exciting target for further research.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.