ArticleJournal of molecular and cellular cardiology2012
Non-neuronal cholinergic machinery present in cardiomyocytes offsets hypertrophic signals.
Article in Journal of molecular and cellular cardiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 107 citations in OpenAlex.
- Context-tuned strategies for marker selection precision in neuronal studies.Frontiers in neuroscience · 2026Review
- Impaired cardiac non-neuronal acetylcholine synthesis triggers mitochondrial dysfunction with the loss of nicotinic receptor-mediated calcium handling, causing the failing heart.Clinical science (London, England : 1979) · 2025Article
- Pyridostigmine Treatment Significantly Alleviates Isoprenaline-Induced Chronic Heart Failure in Rats.International journal of molecular sciences · 2025Article
- A maternal diet high in carbohydrates causes bradyarrhythmias and changes in heart rate variability in the offspring sex-dependent in mice.Laboratory animal research · 2024Article
- Review
- Activation of the nonneuronal cholinergic cardiac system by hypoxic preconditioning protects isolated adult cardiomyocytes from hypoxia/reoxygenation injury.American journal of physiology. Heart and circulatory physiology · 2024Article
- Editorial: The non-neuronal cholinergic system in the cardiovascular system: its influence on the heart, vasculature, and the central nervous system.Frontiers in cardiovascular medicine · 2024Article
- Mini Review: the non-neuronal cardiac cholinergic system in type-2 diabetes mellitus.Frontiers in cardiovascular medicine · 2024Review
- Non-neuronal cholinergic system in the heart influences its homeostasis and an extra-cardiac site, the blood-brain barrier.Frontiers in cardiovascular medicine · 2024Review
- Increased GIRK channel activity prevents arrhythmia in mice with heart failure by enhancing ventricular repolarization.Scientific reports · 2023Article
- DbhNature communications · 2023Article
- Outcomes of hypothalamic oxytocin neuron-driven cardioprotection after acute myocardial infarction.Basic research in cardiology · 2023Article
- Article
- In vivo vesicular acetylcholine transporter density in human peripheral organs: an [EJNMMI research · 2022Article
- Therapeutic Benefits of Pomegranate Flower Extract: A Novel Effect That Reduces Oxidative Stress and Significantly Improves Diastolic Relaxation in Hyperglycemic In Vitro in Rats.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- α7 Nicotinic acetylcholine receptor mediates right ventricular fibrosis and diastolic dysfunction in pulmonary hypertension.JCI insight · 2021Article
- Cholinergic stimulation with pyridostigmine modulates a heart-spleen axis after acute myocardial infarction in spontaneous hypertensive rats.Scientific reports · 2021Article
- Activation of the cardiac non-neuronal cholinergic system prevents the development of diabetes-associated cardiovascular complications.Cardiovascular diabetology · 2021Article
- Non-neuronal cardiac acetylcholine system playing indispensable roles in cardiac homeostasis confers resiliency to the heart.The journal of physiological sciences : JPS · 2021Article
- Characteristic Effects of the Cardiac Non-Neuronal Acetylcholine System Augmentation on Brain Functions.International journal of molecular sciences · 2021Review
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Recent work has provided compelling evidence that increased levels of acetylcholine (ACh) can be protective in heart failure, whereas reduced levels of ACh secretion can cause heart malfunction. Previous data show that cardiomyocytes themselves can actively secrete ACh, raising the question of whether this cardiomyocyte derived ACh may contribute to the protective effects of ACh in the heart. To address the functionality of this non-neuronal ACh machinery, we used cholinesterase inhibitors and a siRNA targeted to AChE (acetylcholinesterase) as a way to increase the availability of ACh secreted by cardiac cells. By using nitric oxide (NO) formation as a biological sensor for released ACh, we showed that cholinesterase inhibition increased NO levels in freshly isolated ventricular myocytes and that this effect was prevented by atropine, a muscarinic receptor antagonist, and by inhibition of ACh synthesis or vesicular storage. Functionally, cholinesterase inhibition prevented the hypertrophic effect as well as molecular changes and calcium transient alterations induced by adrenergic overstimulation in cardiomyocytes. Moreover, inhibition of ACh storage or atropine blunted the anti-hypertrophic action of cholinesterase inhibition. Altogether, our results show that cardiomyocytes possess functional cholinergic machinery that offsets deleterious effects of hyperadrenergic stimulation. In addition, we show that adrenergic stimulation upregulates expression levels of cholinergic components. We propose that this cardiomyocyte cholinergic signaling could amplify the protective effects of the parasympathetic nervous system in the heart and may counteract or partially neutralize hypertrophic adrenergic effects.
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