ArticleJournal of muscle research and cell motility2006
Effect of changes in action potential spike configuration, junctional sarcoplasmic reticulum micro-architecture and altered t-tubule structure in human heart failure.
Article in Journal of muscle research and cell motility, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 101 citations in OpenAlex.
- Excitation and mechanical contraction of a 3D cardiomyocyte model.Biophysical journal · 2025Article
- Electrophysical cardiac remodeling at the molecular level: Insights into ryanodine receptor activation and calcium-induced calcium release from a stochastic explicit-particle model.Biophysical journal · 2024Article
- Mechanisms of spontaneous CaThe Journal of physiology · 2023Article
- Serial block face scanning electron microscopy reveals region-dependent remodelling of transverse tubules post-myocardial infarction.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022Article
- Fibrosis and impaired CaBiophysical reviews · 2022Article
- T-tubule remodeling in human hypertrophic cardiomyopathy.Journal of muscle research and cell motility · 2021Review
- A mouse model of Huntington's disease shows altered ultrastructure of transverse tubules in skeletal muscle fibers.The Journal of general physiology · 2021Article
- SERCA2a ameliorates cardiomyocyte T-tubule remodeling via the calpain/JPH2 pathway to improve cardiac function in myocardial ischemia/reperfusion mice.Scientific reports · 2021Article
- The Physiology and Pathophysiology of T-Tubules in the Heart.Frontiers in physiology · 2021Review
- The architecture and function of cardiac dyads.Biophysical reviews · 2020Review
- Structural variability of dyads relates to calcium release in rat ventricular myocytes.Scientific reports · 2020Article
- Cardiomyocyte damage control in heart failure and the role of the sarcolemma.Journal of muscle research and cell motility · 2019Article
- Modeling Depolarization Delay, Sodium Currents, and Electrical Potentials in Cardiac Transverse Tubules.Frontiers in physiology · 2019Article
- Hyperactive ryanodine receptors in human heart failure and ischaemic cardiomyopathy reside outside of couplons.Cardiovascular research · 2018Article
- Human cardiomyocyte calcium handling and transverse tubules in mid-stage of post-myocardial-infarction heart failure.ESC heart failure · 2018Article
- Shining New Light on the Structural Determinants of Cardiac Couplon Function: Insights From Ten Years of Nanoscale Microscopy.Frontiers in physiology · 2018Review
- Interplay Between Sub-Cellular Alterations of Calcium Release and T-Tubular Defects in Cardiac Diseases.Frontiers in physiology · 2018Article
- Transverse tubule remodelling: a cellular pathology driven by both sides of the plasmalemma?Biophysical reviews · 2017Review
- Regulation of Cardiomyocyte T-Tubular Structure: Opportunities for Therapy.Current heart failure reports · 2017Review
- Post-Myocardial Infarction T-tubules Form Enlarged Branched Structures With Dysregulation of Junctophilin-2 and Bridging Integrator 1 (BIN-1).Journal of the American Heart Association · 2017Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Using a Monte-Carlo model of L-type Ca2+ channel (DHPR) gating, we have examined the effect of changes in the early time course of the action potential as seen in human heart failure on excitation contraction coupling. The time course of DHPR Ca2+ influx was coupled into a simple model of sarcoplasmic reticulum Ca2+ release. Our model shows that the loss of the initial spike in human heart failure should reduce the synchrony of Ca2+ spark production and lead to the appearance of late Ca2+ sparks and greater non-uniformity of intracellular Ca2+. Within the junctional space of the cardiac dyad, a small increase in the mean distance of a DHPR from a RyR results in a marked decrease in the ability of the DHPR-mediated increase in local [Ca2+] concentration to activate RyRs. This suggests that the efficiency of EC coupling may be reduced if changes in micro-architecture develop and such effects have been noted in experimental models of heart failure. High resolution imaging of t-tubules in tachycardia-induced heart failure show deranged t-tubule structure. While in normal human hearts t-tubules run mainly in a radial direction, t-tubules in the heart failure samples were oriented more toward the long axis of the cell. In addition, t-tubules may become dilated and bifurcated. Our data suggest that changes in the micro-architecture of the cell and membrane structures associated with excitation-contraction coupling, combined with changes in early action potential configuration can reduce the efficiency by which Ca2+ influx via DHPRs can activate SR calcium release and cardiac contraction. While the underlying cause of these effects is unclear, our data suggest that geometric factors can play an important role in the pathophysilogy of the human heart in failure.
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