ArticleScience signaling2014
Mechanochemotransduction during cardiomyocyte contraction is mediated by localized nitric oxide signaling.
Article in Science signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 137 citations in OpenAlex.
- Stretch-Induced Increase in CaJournal of the American Heart Association · 2025Article
- Excitation and mechanical contraction of a 3D cardiomyocyte model.Biophysical journal · 2025Article
- Modeling autoregulation of cardiac excitation-Ca-contraction and arrhythmogenic activities in response to mechanical load changes.iScience · 2025Article
- The Heart Is a Smart Pump: Mechanotransduction Mechanisms of the Frank-Starling Law and the Anrep Effect.Annual review of physiology · 2025Review
- Early pathological mechanisms in a mouse model of heart failure with preserved ejection fraction.American journal of physiology. Heart and circulatory physiology · 2024Article
- Mechanisms of stretch-induced electro-anatomical remodeling and atrial arrhythmogenesis.Journal of molecular and cellular cardiology · 2024Review
- The NADPH oxidase inhibitor diphenyleneiodonium suppresses CaThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2024Article
- Dynamic control of contractile resistance to iPSC-derived micro-heart muscle arrays.Journal of biomedical materials research. Part A · 2024Article
- High-content method for mechanosignaling studies using IsoStretcher technology and quantitative CaCellular and molecular life sciences : CMLS · 2024Article
- Architecture design and advanced manufacturing of heart-on-a-chip: scaffolds, stimulation and sensors.Microsystems & nanoengineering · 2024Review
- NADPH Oxidases and Oxidative Stress in the Pathogenesis of Atrial Fibrillation.Antioxidants (Basel, Switzerland) · 2023Review
- Dynamic mechanobiology of cardiac cells and tissues: Current status and future perspective.Biophysics reviews · 2023Review
- Nitrosylation of cardiac CaMKII at Cys290 mediates mechanical afterload-induced increases in CaThe Journal of physiology · 2022Article
- Extracellular stiffness induces contractile dysfunction in adult cardiomyocytes via cell-autonomous and microtubule-dependent mechanisms.Basic research in cardiology · 2022Article
- Modeling cardiomyocyte mechanics and autoregulation of contractility by mechano-chemo-transduction feedback.iScience · 2022Article
- Cardiomyocyte Microtubules: Control of Mechanics, Transport, and Remodeling.Annual review of physiology · 2022Review
- Article
- Chemogenetic Approaches to Probe Redox Pathways: Implications for Cardiovascular Pharmacology and Toxicology.Annual review of pharmacology and toxicology · 2022Article
- Stop the beat to see the rhythm: excitation-contraction uncoupling in cardiac research.American journal of physiology. Heart and circulatory physiology · 2021Review
- Towards precision medicine in heart failure.Nature reviews. Cardiology · 2021Review
28 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 3 institutions in 1 country.
Funding
Abstract
Cardiomyocytes contract against a mechanical load during each heartbeat, and excessive mechanical stress leads to heart diseases. Using a cell-in-gel system that imposes an afterload during cardiomyocyte contraction, we found that nitric oxide synthase (NOS) was involved in transducing mechanical load to alter Ca(2+) dynamics. In mouse ventricular myocytes, afterload increased the systolic Ca(2+) transient, which enhanced contractility to counter mechanical load but also caused spontaneous Ca(2+) sparks during diastole that could be arrhythmogenic. The increases in the Ca(2+) transient and sparks were attributable to increased ryanodine receptor (RyR) sensitivity because the amount of Ca2(+) in the sarcoplasmic reticulum load was unchanged. Either pharmacological inhibition or genetic deletion of nNOS (or NOS1), but not of eNOS (or NOS3), prevented afterload-induced Ca2(+) sparks. This differential effect may arise from localized NO signaling, arising from the proximity of nNOS to RyR, as determined by super-resolution imaging. Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) and nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) also contributed to afterload-induced Ca(2+) sparks. Cardiomyocytes from a mouse model of familial hypertrophic cardiomyopathy exhibited enhanced mechanotransduction and frequent arrhythmogenic Ca(2+) sparks. Inhibiting nNOS and CaMKII, but not NOX2, in cardiomyocytes from this model eliminated the Ca2(+) sparks, suggesting mechanotransduction activated nNOS and CaMKII independently from NOX2. Thus, our data identify nNOS, CaMKII, and NOX2 as key mediators in mechanochemotransduction during cardiac contraction, which provides new therapeutic targets for treating mechanical stress-induced Ca(2+) dysregulation, arrhythmias, and cardiomyopathy.
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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.