ArticleEuropean heart journal2025
An endogenous cholinergic system controls electrical conduction in the heart.
Article in European heart journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Long-Term Cardiovascular Risks of Anticholinergic Versus Non-Anticholinergic Antidepressants: A Target Trial Emulation With Negative Control Correction.Pharmacoepidemiology and drug safety · 2026Article
- Varenicline-mediated cholinergic activation through α4β2 nAChR inhibits microglial neuroinflammation and alleviates neuropathic pain and depression following spinal cord injury.Journal of translational medicine · 2026Article
- Acetylcholine in Brain-Body Communication: Biological Mechanisms and Physiological Roles.International journal of molecular sciences · 2026Review
- Anticholinergic drug burden and incident cardiovascular events: a population-based study.BMC medicine · 2026Article
- Cardiac endogenous transmitter system: molecular features, functions, and clinical implications.European heart journal · 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
- The endogenous cholinergic system overwhelmingly predominates over the exogenous system in regulating ventricular bioelectrical homeostasis.European heart journal · 2025Article
- Non-neuronal ventricular cardiomyocyte-located nicotinergic acetylcholine receptors cause remodelling and arrhythmias.European heart journal · 2025Article
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Authors and funding
16 authors.
Funding
Abstract
BACKGROUND AND
aimsThe cholinergic system is distributed in the nervous system, mediating electrical conduction through acetylcholine (ACh). This study aims to identify whether the heart possesses an intact endogenous cholinergic system and to explore its electrophysiological functions and relationship with arrhythmias in both humans and animals.
methodsThe components of the heart's endogenous cholinergic system were identified by a combination of multiple molecular cell biology techniques. The relationship of this system with cardiac electrical conduction and arrhythmias was analysed through electrophysiological techniques.
resultsAn intact cholinergic system including ACh, ACh transmitter vesicles, ACh transporters, ACh metabolic enzymes, and ACh receptors was identified in both human and mouse ventricular cardiomyocytes (VCs). The key components of the system significantly regulated the conductivity of electrical excitation among VCs. The influence of this system on electrical excitation conduction was further confirmed both in the mice with α4 or α7 nicotinic ACh receptors (nAChRs) knockouts and in the monolayers of human induced pluripotent stem cell-derived cardiomyocytes. Mechanistically, ACh induced an inward current through nAChRs to reduce the minimum threshold current required to generate an action potential in VCs, thereby enhancing the excitability that acts as a prerequisite for electrical conduction. Importantly, defects in this system were associated with fatal ventricular arrhythmias in both patients and mice.
conclusionsThis study identifies an integrated cholinergic system inherent to the heart, rather than external nerves that can effectively control cardiac electrical conduction. The discovery reveals arrhythmia mechanisms beyond classical theories and opens new directions for arrhythmia research.
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