Evidence mapPaperPMID 39437249Full record

ArticleEuropean heart journal2025

An endogenous cholinergic system controls electrical conduction in the heart.

Duanyang Xie, Ke Xiong, Nianguo Dong, Guanghua Wang, Qicheng Zou, Beihua Shao, Zhiwen Chen, Luxin Wang, Yu Kong, Xu Wang and 6 more

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Duanyang XieState Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China.ORCID 0000-0002-2651-2202
Ke XiongState Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China.
Nianguo DongDepartment of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.ORCID 0000-0001-5437-599X
Guanghua WangState Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China.
Qicheng ZouState Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China.
Beihua ShaoState Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China.
Zhiwen ChenState Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China.
Luxin WangDepartment of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China.
Yu KongElectron Microscopy Facilities of Center for Excellence in Brain Science and Technology, Chinese Academy of Science, Shanghai 200031, China.
Xu WangElectron Microscopy Facilities of Center for Excellence in Brain Science and Technology, Chinese Academy of Science, Shanghai 200031, China.
Xuling SuDepartment of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China.
Wenli BaiState Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China.
Jian YangState Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China.
Yi LiuState Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China.
Bin ZhouCenter for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China.
Yi-Han ChenState Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China.

Funding

Fundamental Research Funds for the Central UniversitiesKey Research Center Construction Project of Shanghai 2022ZZ01008National Natural Science Foundation of China 82088101National Research and Development Plan 2019YFA0801501Research Unit of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences 2019RU045Top-level Clinical Discipline Project of Shanghai Pudong PWYgf2021-01
6 · The paper itself

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.

Indexed as

AcetylcholineArrhythmias, CardiacHeart Conduction SystemMyocytes, CardiacAction PotentialsAnimalsHumansMaleMiceMice, KnockoutReceptors, CholinergicReceptors, NicotinicAcetylcholineReceptors, CholinergicReceptors, NicotinicArrhythmiasCholinergic systemConductivityElectrophysiologyExcitabilityHeart

Identifiers

PMID39437249
PMCPMC11959186

What Socratic holds

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Registered trials

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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 Socratic graph.