Innervation and Neuronal Control of the Mammalian Sinoatrial Node a Comprehensive Atlas Article Swipe
Peter Hanna
,
Michael J. Dacey
,
Jaclyn A. Brennan
,
Alison Moss
,
Shaina Robbins
,
Sirisha Achanta
,
Natália P. Biscola
,
Mohammed Amer Swid
,
Pradeep S. Rajendran
,
Shumpei Mori
,
Joseph Hadaya
,
Elizabeth Smith
,
Stanley G. Peirce
,
Jin Chen
,
Leif A. Havton
,
Zixi Cheng
,
Rajanikanth Vadigepalli
,
James S. Schwaber
,
Robert L. Lux
,
Igor R. Efimov
,
John D. Tompkins
,
Donald B. Hoover
,
Jeffrey L. Ardell
,
Kalyanam Shivkumar
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1161/circresaha.120.318458
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1161/circresaha.120.318458
Rationale: Cardiac function is under exquisite intrinsic cardiac neural control. Neuroablative techniques to modulate control of cardiac function are currently being studied in patients, albeit with variable and sometimes deleterious results. Objective: Recognizing the major gaps in our understanding of cardiac neural control, we sought to evaluate neural regulation of impulse initiation in the sinoatrial node (SAN) as an initial discovery step. Methods and Results: We report an in-depth, multiscale structural and functional characterization of the innervation of the SAN by the right atrial ganglionated plexus (RAGP) in porcine and human hearts. Combining intersectional strategies, including tissue clearing, immunohistochemical, and ultrastructural techniques, we have delineated a comprehensive neuroanatomic atlas of the RAGP-SAN complex. The RAGP shows significant phenotypic diversity of neurons while maintaining predominant cholinergic innervation. Cellular and tissue-level electrophysiological mapping and ablation studies demonstrate interconnected ganglia with synaptic convergence within the RAGP to modulate SAN automaticity, atrioventricular conduction, and left ventricular contractility. Using this approach, we comprehensively demonstrate that intrinsic cardiac neurons influence the pacemaking site in the heart. Conclusions: This report provides an experimental demonstration of a discrete neuronal population controlling a specific geographic region of the heart (SAN) that can serve as a framework for further exploration of other parts of the intrinsic cardiac nervous system (ICNS) in mammalian hearts and for developing targeted therapies.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1161/circresaha.120.318458
- https://www.ahajournals.org/doi/pdf/10.1161/CIRCRESAHA.120.318458
- OA Status
- bronze
- Cited By
- 105
- References
- 91
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3131160888
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W3131160888Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1161/circresaha.120.318458Digital Object Identifier
- Title
-
Innervation and Neuronal Control of the Mammalian Sinoatrial Node a Comprehensive AtlasWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-02-25Full publication date if available
- Authors
-
Peter Hanna, Michael J. Dacey, Jaclyn A. Brennan, Alison Moss, Shaina Robbins, Sirisha Achanta, Natália P. Biscola, Mohammed Amer Swid, Pradeep S. Rajendran, Shumpei Mori, Joseph Hadaya, Elizabeth Smith, Stanley G. Peirce, Jin Chen, Leif A. Havton, Zixi Cheng, Rajanikanth Vadigepalli, James S. Schwaber, Robert L. Lux, Igor R. Efimov, John D. Tompkins, Donald B. Hoover, Jeffrey L. Ardell, Kalyanam ShivkumarList of authors in order
- Landing page
-
https://doi.org/10.1161/circresaha.120.318458Publisher landing page
- PDF URL
-
https://www.ahajournals.org/doi/pdf/10.1161/CIRCRESAHA.120.318458Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
bronzeOpen access status per OpenAlex
- OA URL
-
https://www.ahajournals.org/doi/pdf/10.1161/CIRCRESAHA.120.318458Direct OA link when available
- Concepts
-
Sinoatrial node, Neuroscience, Atrioventricular node, Cardiac electrophysiology, Contractility, Electrophysiology, Biology, Electrical conduction system of the heart, Cholinergic, Population, Medicine, Anatomy, Internal medicine, Electrocardiography, Tachycardia, Heart rate, Blood pressure, Environmental healthTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
105Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 17, 2024: 26, 2023: 25, 2022: 24, 2021: 13Per-year citation counts (last 5 years)
- References (count)
-
91Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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