ArticleJournal of molecular and cellular cardiology2010
Calcium sensitivity and the Frank-Starling mechanism of the heart are increased in titin N2B region-deficient mice.
Article in Journal of molecular and cellular cardiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 55 citations in OpenAlex.
- Diastolic contributors in cardiomyocytes of a cardiometabolic HFpEF-like mouse model.The Journal of general physiology · 2026Article
- Titin's P-zone domains A164-167 are essential for thick filament structural arrangement.The Journal of general physiology · 2026Article
- Rbm20 antisense oligonucleotides alleviate diastolic dysfunction in a mouse model of cardiometabolic heart failure (HFpEF).Cardiovascular research · 2025Article
- TTN:c.12478del in proximal I-band of titin represents a common molecular cause of dilated cardiomyopathy in Slovenian patients.Orphanet journal of rare diseases · 2025Article
- Modeling cardiomyocyte signaling and metabolism predicts genotype-to-phenotype mechanisms in hypertrophic cardiomyopathy.Computers in biology and medicine · 2024Article
- Structural domain in the Titin N2B-us region binds to FHL2 in a force-activation dependent manner.Nature communications · 2024Article
- N-terminal truncated cardiac troponin I enhances Frank-Starling response by increasing myofilament sensitivity to resting tension.The Journal of general physiology · 2023Article
- Titin (TTN): from molecule to modifications, mechanics, and medical significance.Cardiovascular research · 2022Review
- Cardiac efficiency and Starling's Law of the Heart.The Journal of physiology · 2022Article
- Shortening the thick filament by partial deletion of titin's C-zone alters cardiac function by reducing the operating sarcomere length range.Journal of molecular and cellular cardiology · 2022Article
- The titin N2B and N2A regions: biomechanical and metabolic signaling hubs in cross-striated muscles.Biophysical reviews · 2021Review
- High efficiency preparation of skinned mouse cardiac muscle strips from cryosections for contractility studies.Experimental physiology · 2020Article
- Getting into the thick (and thin) of it.The Journal of general physiology · 2019Article
- A short history of the development of mathematical models of cardiac mechanics.Journal of molecular and cellular cardiology · 2019Review
- Sarcomere length-dependent effects on CaThe Journal of general physiology · 2019Article
- Organ-level right ventricular dysfunction with preserved Frank-Starling mechanism in a mouse model of pulmonary arterial hypertension.Journal of applied physiology (Bethesda, Md. : 1985) · 2018Article
- Tampering with springs: phosphorylation of titin affecting the mechanical function of cardiomyocytes.Biophysical reviews · 2017Review
- Distinct contributions of the thin and thick filaments to length-dependent activation in heart muscle.eLife · 2017Article
- Reducing RBM20 activity improves diastolic dysfunction and cardiac atrophy.Journal of molecular medicine (Berlin, Germany) · 2016Article
- Maturing human pluripotent stem cell-derived cardiomyocytes in human engineered cardiac tissues.Advanced drug delivery reviews · 2016Review
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Previous work suggests that titin-based passive tension is a factor in the Frank-Starling mechanism of the heart, by increasing length-dependent activation (LDA) through an increase in calcium sensitivity at long sarcomere length. We tested this hypothesis in a mouse model (N2B KO model) in which titin-based passive tension is elevated as a result of the excision of the N2B element, one of cardiac titin's spring elements. LDA was assessed by measuring the active tension-pCa (-log[Ca(2+)]) relationship at sarcomere length (SLs) of 1.95, 2.10, and 2.30 microm in WT and N2B KO skinned myocardium. LDA was positively correlated with titin-based passive tension due to an increase in calcium sensitivity at the longer SLs in the KO. For example, at pCa 6.0, the KO:WT tension ratio was 1.28+/-0.07 and 1.42+/-0.04 at SLs of 2.1 and 2.3 microm, respectively. There was no difference in protein expression or total phosphorylation of sarcomeric proteins. We also measured the calcium sensitivity after PKA treating the skinned muscle and found that titin-based passive tension was also now correlated with LDA, with a slope that was significantly increased compared to no PKA treatment. Finally, we performed isolated heart experiments and measured the Frank-Starling relation (slope of developed wall stress-LV volume relation) as well as diastolic stiffness (slope of diastolic wall stress-volume relation). The FSM was more pronounced in the N2B KO hearts and the slope of the FSM correlated with diastolic stiffness. These findings support that titin-based passive tension triggers an increase in calcium sensitivity at long sarcomere length, thereby playing an important role in the Frank-Starling mechanism of the heart.
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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.