Comparative specialization of intrinsic cardiac neurons in humans, mice and pigs.

Autor: Tompkins JD; UCLA Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, David Geffen School of Medicine at UCLA, Los Angeles, California, USA., Hoover DB; Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA., Havton LA; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Patel JC; UCLA Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, David Geffen School of Medicine at UCLA, Los Angeles, California, USA., Cho Y; UCLA Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, David Geffen School of Medicine at UCLA, Los Angeles, California, USA., Smith EH; Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA., Biscola NP; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Ajijola OA; UCLA Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, David Geffen School of Medicine at UCLA, Los Angeles, California, USA., Shivkumar K; UCLA Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, David Geffen School of Medicine at UCLA, Los Angeles, California, USA., Ardell JL; UCLA Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Jazyk: angličtina
Zdroj: The Journal of physiology [J Physiol] 2024 Nov 08. Date of Electronic Publication: 2024 Nov 08.
DOI: 10.1113/JP286714
Abstrakt: Intrinsic cardiac neurons (ICNs) play a crucial role in the proper functioning of the heart; yet a paucity of data pertaining to human ICNs exist. We took a multidisciplinary approach to complete a detailed cellular comparison of the structure and function of ICNs from mice, pigs and humans. Immunohistochemistry of whole and sectioned ganglia, transmission electron microscopy, intracellular microelectrode recording and dye filling for quantitative morphometry were used to define the neurophysiology, histochemistry and ultrastructure of these neurons across species. The densely packed, smaller ICNs of mouse lacked dendrites, formed axosomatic connections and had high synaptic efficacy constituting an obligatory synapse. At pig ICNs, a convergence of subthreshold cholinergic inputs onto extensive dendritic arbors supported greater summation and integration of synaptic input. Human ICNs were tonically firing, with synaptic stimulation evoking large suprathreshold EPSPs like mouse, and subthreshold potentials like pig. Ultrastructural examination of synaptic terminals revealed conserved architecture, yet small clear vesicles were larger in pigs and humans. The presence and localization of ganglionic neuropeptides was distinct, with abundant vasoactive intestinal polypeptide observed in human but not pig or mouse ganglia, and little substance P or calcitonin gene-related peptide in pig ganglia. Action potential waveforms were similar, but human ICNs had larger after-hyperpolarizations. Intrinsic excitability differed; 95% of human neurons were tonic, all pig neurons were phasic, and both phasic and tonic phenotypes were observed in mouse. In combination, this publicly accessible, multimodal atlas of ICNs from mice, pigs and humans identifies similarities and differences in the evolution of ICNs. KEY POINTS: Intrinsic cardiac neurons (ICNs) are essential to the regulation of cardiac function. We investigated the neurochemistry, morphology, ultrastructure, membrane physiology and synaptic transmission of ICNs from donated human hearts in parallel with identical studies of ICNs from mice and pigs to create a publicly accessible cellular atlas detailing the structure and function of these neurons across species. In addition to presenting foundational data on human ICNs, this comparative study identifies both conserved and derived attributes of these neurons within mammals. The findings have significant implications for understanding the regulation of cardiac autonomic function in humans and may greatly influence strategies for neuromodulation in conditions such as atrial fibrillation and heart failure.
(© 2024 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)
Databáze: MEDLINE
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