Connexin 43 expression delineates two discrete pathways in the human atrioventricular junction
Open accessAbstract
Gap junction expression has been studied in the atrioventricular junction (AVJ) of many species, however, their distribution in the human AVJ is unknown. The AVJ expression of the gap junction protein connexin 43 (Cx43) is species dependent; therefore we investigated its distribution in the human AVJ. Using Masson trichrome histology, we reconstructed the AVJ of three normal human hearts and one with dilated cardiomyopathy in three dimensions. Cx43 was immunolabeled with vimentin and alpha-actinin to determine the cellular origin of Cx43 and was quantified in the following structures: interatrial septum (IAS), His bundle, compact node (CN), lower nodal bundle (LNB), leftward and rightward nodal extensions (LE and RE), and inferior, endocardial, and left-sided transitional cells. Histology revealed two nodal extensions in three of four hearts. Cx43 was found in the myocytes, but not fibroblasts, of the AVJ. LE and CN Cx43 was lower than the IAS (P < 0.05) and the RE, LNB, and His all expressed Cx43 similarly, with approximately half of IAS expression (RE: 44 +/- 36%; LNB: 50 +/- 26%; His: 48 +/- 12%, P = NS compared with IAS). Cx43 levels in transitional cells were similar to the IAS (P = not significant). Cx43 was found in myocytes of the human AVJ, and its expression pattern delineates two separate continuous structures: one consists of the LE and CN with little Cx43, and the other consists of the His, LNB, and RE expressing approximately half the Cx43 of the IAS. The differential Cx43 expression may provide each structure with unique conduction properties, contributing to arrhythmias arising from the AVJ.
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The AV node is a three-dimensional structure with greater variability in tissue space constant and poor gap junction connectivity due to differential connexin isoform expression, conditions that explain dual conduction and nodal reentrant arrhythmogenesis.
“The AV node is a three-dimensional structure with greater variability in the space constant of tissue, and poor gap junction connectivity due to differential expression of connexin isoforms, conditions that provide an explanation of dual conduction and nodal reentrant arrhythmogenesis.218,219”
From European Heart Rhythm Association (EHRA) consensus document on the management of supraventricular arrhythmias, endorsed by Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulacion Cardiaca y Electrofisiologia (SOLAECE) (2017) · cites this paper as [219]
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- Authors
- Hucker, W. J., Mccain, M. L., Laughner, J. I., Iaizzo, P. A., & Efimov, I. R.
- Affiliations
- Washington University in St. Louis (US)
- University of Minnesota (US)
- Corresponding author
- Efimov, Igor R.
- Venue
- The Anatomical Record
- Publisher
- Wiley
- Published
- 2007-12-17
- Volume
- 291
- Issue
- 2
- Pages
- 204-215
- ISSN
- 1932-8486 (ISSN-L)
- 1932-8494
- PMC
- PMC2756604
- OpenAlex
- W2118338652
- Cited by
- 106
- References
- 35
- Citations by year
- 2026: 8 · 2025: 4 · 2024: 9 · 2023: 2 · 2022: 1 · 2021: 6 · 2020: 4 · 2019: 4 · 2018: 8 · 2017: 9 · 2016: 3 · 2015: 4 · 2014: 3 · 2013: 10 · 2012: 8
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Anatomical Record (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL085369, R01HL114395)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac pacing and defibrillation studies
- Keywords
- connexin 43, atrioventricular junction, gap junctions, human heart, His bundle, interatrial septum, transitional cells, cardiac conduction, dilated cardiomyopathy, cardiac arrhythmias, 3D reconstruction
- MeSH terms
- Adult, Aged, Azo Compounds, Coloring Agents, Eosine Yellowish-(YS), Fibroblasts, Fluorescent Antibody Technique, Heart Conduction System, Humans, Male, Methyl Green, Middle Aged, Connexin 43, Imaging, Three-Dimensional, Myocytes, Cardiac
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