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The role of the tripartite synapse in the heart: How glial cells may contribute to the physiology and pathophysiology of the intracardiac nervous system.

  • Tedoldi, Angelo1
  • Argent, Liam1
  • Montgomery, Johanna M1
  • 1 Department of Physiology and Manaaki Mānawa Centre for Heart Research University of Auckland, New Zealand. , (New Zealand)
Published Article
AJP Cell Physiology
American Physiological Society
Publication Date
Oct 21, 2020
DOI: 10.1152/ajpcell.00363.2020
PMID: 33085497


One of the major roles of the intracardiac nervous system (ICNS) is to act as the final site of signal integration for efferent information destined for the myocardium to enable local control of heart rate and rhythm. Multiple subtypes of neurons exist in the ICNS where they are organised into clusters termed ganglionated plexi (GP). The majority of cells in the ICNS are actually glial cells, however, despite this ICNS glial cells have received little attention to date. In the central nervous system where glial cell function has been widely studied, glia are no longer viewed simply as supportive cells, but rather have been shown to play an active role in modulating neuronal excitability and synaptic plasticity. Pioneering studies have demonstrated that as well as glia within the brainstem, glial cells within multiple autonomic ganglia in the peripheral nervous system, including the ICNS, can also act to modulate cardiovascular function. Clinically, atrial fibrillation (AF) patients undergoing catheter ablation show high plasma levels of S100B, a protein produced by cardiac glial cells, correlate with decreased AF recurrence. Interestingly, S100B also alters GP neuron excitability and neurite outgrowth in the ICNS. These studies highlight the importance of understanding how glial cells can affect the heart by modulating GP neuron activity or synaptic inputs. Here, we review studies investigating glia both in the central and peripheral nervous systems to discuss the potential role of glia in controlling cardiac function in health and disease, paying particular attention to the glial cells of the ICNS.

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