The Role of Neuro-Cardiac Junctionsin Sympathetic Regulation of the Heart

One of the important mechanisms of cardiac regulation is realized via sympathetic innervation of cardiac myocytes. Axons of the sympathetic neurons branch out and form varicosities along their length, filled with synaptic vesicles that contain a major neurotransmitter (norepinephrine) and co-neurotransmitters. The varicosities may closely contact with cardiomyocytes and form neuro-cardiac junctions (NCJs), which have a synapse-like organization, namely pre- and postsynaptic regions separated by a narrow gap. These synaptic structures demonstrate high plasticity, while neurotransmitter release from the presynaptic varicosity is tightly regulated, including due to autoreceptors. Neurotransmission via NCJs mediates fast chronotropic and inotropic effects and also controls tropic processes, which determine the size of cardiomyocytes and the architecture of the heart wall. Different subtypes of postsynaptic adrenoceptors are involved in these short- and long-term effects of neuro-cardiac interactions. Changes in cardiac adrenergic neurotransmission often accompany many widespread pathologies, such as heart failure, arrhythmias and hypertension, contributing to their progression. In this review, we systematized and summarized experimental evidence supporting the hypothesis about cardiac quasi-synaptic transmission that may be of decisive importance for brain-heart communication.