ArticleThe Journal of physiology2018
Dynamics of neuroeffector coupling at cardiac sympathetic synapses.
Article in The Journal of physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed.
- Innervated human cardiac muscle model reveals sympathetic drivers of KCNH2-associated arrhythmias.Nature communications · 2026Article
- A reproducible and physiologically relevant human iPSC-derived platform for in vitro modeling of the neurocardiac junction.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- OPA1 Deficiency Impairs NGF Signaling and Drives Sympathetic Neurodegeneration.JACC. Basic to translational science · 2026Article
- Development and modeling of cardiac autonomic innervation.Nature cardiovascular research · 2025Review
- Article
- Sympathetic neurons can modify the intrinsic structural and functional properties of human pluripotent stem cell-derived cardiomyocytes.The Journal of physiology · 2025Article
- Cardiac sympathetic neurons are additional cells affected in genetically determined arrhythmogenic cardiomyopathy.The Journal of physiology · 2025Article
- Molecular and cellular neurocardiology in heart disease.The Journal of physiology · 2025Review
- Neurocardiology: translational advancements and potential.The Journal of physiology · 2025Review
- Advancing organ-on-chip systems: the role of microfluidics in neuro-cardiac research.Current research in pharmacology and drug discovery · 2025Review
- Chronic nicotine exposure is associated with electrophysiological and sympathetic remodeling in the intact rabbit heart.American journal of physiology. Heart and circulatory physiology · 2024Article
- Cardiac optogenetics: shining light on signaling pathways.Pflugers Archiv : European journal of physiology · 2023Review
- DbhNature communications · 2023Article
- Opto-SICM framework combines optogenetics with scanning ion conductance microscopy for probing cell-to-cell contacts.Communications biology · 2023Article
- Diversity of cells and signals in the cardiovascular system.The Journal of physiology · 2023Article
- Topographical mapping of catecholaminergic axon innervation in the flat-mounts of the mouse atria: a quantitative analysis.Scientific reports · 2023Article
- Wireless Self-Powered Optogenetic System for Long-Term Cardiac Neuromodulation to Improve Post-MI Cardiac Remodeling and Malignant Arrhythmia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Sympathetic neuropathology is revealed in muscles affected by amyotrophic lateral sclerosis.Frontiers in physiology · 2023Article
- Impact of Neurons on Patient-Derived Cardiomyocytes Using Organ-On-A-Chip and iPSC Biotechnologies.Cells · 2022Article
- Neurotoxic Effect of Doxorubicin Treatment on Cardiac Sympathetic Neurons.International journal of molecular sciences · 2022Article
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10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
key pointsThe present study demonstrates, by in vitro and in vivo analyses, the novel concept that signal transmission between sympathetic neurons and the heart, underlying the physiological regulation of cardiac function, operates in a quasi-synaptic fashion. This is a result of the direct coupling between neurotransmitter releasing sites and effector cardiomyocyte membranes. ABSTRACT: Cardiac sympathetic neurons (SNs) finely tune the rate and strength of heart contractions to match blood demand, both at rest and during acute stress, through the release of noradrenaline (NE). Junctional sites at the interface between the two cell types have been observed, although whether direct neurocardiac coupling has a role in heart physiology has not been clearly demonstrated to date. We investigated the dynamics of SN/cardiomyocyte intercellular signalling, both by fluorescence resonance energy transfer-based imaging of cAMP in co-cultures, as a readout of cardiac β-adrenergic receptor activation, and in vivo, using optogenetics in transgenic mice with SN-specific expression of Channelrhodopsin-2. We demonstrate that SNs and cardiomyocytes interact at specific sites in the human and rodent heart, as well as in co-cultures. Accordingly, neuronal activation elicited intracellular cAMP increases only in directly contacted myocytes and cell-cell coupling utilized a junctional extracellular signalling domain with an elevated NE concentration. In the living mouse, optogenetic activation of cardiac SNs innervating the sino-atrial node resulted in an instantaneous chronotropic effect, which shortened the heartbeat interval with single beat precision. Remarkably, inhibition of the optogenetically elicited chronotropic responses required a high dose of propranolol (20-50 mg kg
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