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An endogenous cholinergic system controls electrical conduction in the heart.

Duanyang Xie1,2,3,4, Ke Xiong1,3, Nianguo Dong5

  • 1State Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China.

European Heart Journal
|October 22, 2024
PubMed
Summary

The heart has its own cholinergic system, using acetylcholine (ACh) to regulate electrical conduction and excitability. Defects in this system are linked to fatal ventricular arrhythmias in humans and animals.

Keywords:
ArrhythmiasCholinergic systemConductivityElectrophysiologyExcitabilityHeart

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Area of Science:

  • Cardiovascular Physiology
  • Neurobiology
  • Molecular Cardiology

Background:

  • The nervous system utilizes the cholinergic system, mediated by acetylcholine (ACh), for electrical signaling.
  • The presence and function of an endogenous cardiac cholinergic system were previously unestablished.

Purpose of the Study:

  • To determine if the heart contains an intact endogenous cholinergic system.
  • To investigate the electrophysiological roles of this system.
  • To explore its connection to cardiac arrhythmias.

Main Methods:

  • Utilized molecular and cell biology techniques to identify cholinergic system components in cardiac cells.
  • Employed electrophysiological methods to analyze the system's impact on electrical conduction and arrhythmias.
  • Confirmed findings using knockout mouse models and human induced pluripotent stem cell-derived cardiomyocytes.

Main Results:

  • Identified a complete endogenous cholinergic system within human and mouse ventricular cardiomyocytes.
  • Demonstrated that this system significantly modulates electrical excitation conductivity.
  • Showed that acetylcholine enhances ventricular cardiomyocyte excitability via nicotinic ACh receptors (nAChRs).
  • Linked defects in this system to severe ventricular arrhythmias in both human patients and animal models.

Conclusions:

  • Established the existence of an intrinsic cardiac cholinergic system independent of external nerves.
  • Revealed novel mechanisms underlying cardiac arrhythmias.
  • Opened new avenues for research into arrhythmia pathogenesis and treatment.