Muscarinic acetylcholine receptors M2 are upregulated in the atrioventricular nodal tract in horses with a high burden of second-degree atrioventricular block.
Abstract: Second-degree atrioventricular (AV) block at rest is very common in horses. The underlying molecular mechanisms are unexplored, but commonly attributed to high vagal tone. Unassigned: To assess whether AV block in horses is due to altered expression of the effectors of vagal signalling in the AV node, with specific emphasis on the muscarinic acetylcholine receptor (M) and the G protein-gated inwardly rectifying K (GIRK4) channel that mediates the cardiac current. Unassigned: Eighteen horses with a low burden of second-degree AV block (median 8 block per 20 h, IQR: 32 per 20 h) were assigned to the , while 17 horses with a high burden of second-degree AV block (median: 408 block per 20 h, IQR: 1,436 per 20 h) were assigned to the . Radiotelemetry ECG recordings were performed to assess PR interval and incidence of second-degree AV block episodes at baseline and on pharmacological blockade of the autonomic nervous system (ANS). Wenckebach cycle length was measured by intracardiac pacing ( = 16). Furthermore, the expression levels of the M receptor and the GIRK4 subunit of the I channel were quantified in biopsies from the right atrium, the AV node and right ventricle using immunohistochemistry and machine learning-based automated segmentation analysis ( = 9 + 9). Unassigned: The AV block group had a significantly longer PR interval (mean ± SD, 0.40 ± 0.05 s; < 0.001) and a longer Wenckebach cycle length (mean ± SD, 995 ± 86 ms; = 0.007) at baseline. After blocking the ANS, all second-degree AV block episodes were abolished, and the difference in PR interval disappered ( = 0.80). The AV block group had significantly higher expression of the M receptor ( = 0.02), but not the GIRK4 ( = 0.25) in the AV node compared to the control group. Both M and GIRK4 were highly expressed in the AV node and less expressed in the atria and the ventricles. Unassigned: Here, we demonstrate the involvement of the mR- pathway in underlying second-degree AV block in horses. The high expression level of the M receptor may be responsible for the high burden of second-degree AV blocks seen in some horses.
© 2023 Nissen, Saljic, Carstensen, Braunstein, Hesselkilde, Kjeldsen, Hopster-Iversen, D'Souza, Jespersen and Buhl.
Publication Date: 2023-11-16 PubMed ID: 38034369PubMed Central: PMC10687567DOI: 10.3389/fcvm.2023.1102164Google Scholar: Lookup
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- Journal Article
Summary
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The research investigates the underlying causes of second-degree atrioventricular block in horses, focusing on the role of muscarinic acetylcholine receptors and to a lesser extent, G protein-gated inwardly rectifying potassium channels. It finds that an increased presence of these receptors may contribute to this common equine heart condition.
Background and Purpose
- The study wants to understand more about the second-degree atrioventricular (AV) block in horses, which is often attributed to high vagal tone. The focus is on the factors involved in vagal signaling in the AV node, namely the muscarinic acetylcholine receptor (M) and the G protein-gated inwardly rectifying K (GIRK4) channel.
- The AV block is common in horses and can significantly affect a horse’s performance and well-being. However, the exact molecular mechanisms causing this condition are still unclear.
Methodology
- The experimentation involved two groups of horses: 18 horses with a low burden of AV block and 17 horses with a high burden of AV block.
- Radiotelemetry ECG recordings were done to measure the heart rhythm of the horses both under normal conditions and under pharmacological blockade of the autonomic nervous system (ANS).
- The researchers specifically measured the incidence of AV block episodes and the length of the Wenckebach cycle, a cycle concerning cardiac conduction.
- Simultaneously, levels of M receptor and GIRK4 channel expression were examined in the heart tissue samples from the right atrium, the AV node, and the right ventricle.
Findings
- The horses with a higher burden of second-degree AV block exhibited a longer PR interval and Wenckebach cycle length, indicators of abnormal heart function. However, these differences in heart function disappeared when the ANS was pharmacologically blocked.
- Most notably, the high AV block group showed higher expression levels of the M receptor in the AV node as compared to the control group. Levels of GIRK4 expression, on the other hand, did not show a significant difference.
Conclusion
- The research concludes that an upregulated presence of M receptors in the AV node could be responsible for the high rate of second-degree AV block episodes in horses.
- By examining expression levels of M receptors, the study demonstrates the role of the muscarinic acetylcholine receptor pathway in the pathology of second-degree AV block in horses.
Cite This Article
APA
Nissen SD, Saljic A, Carstensen H, Braunstein TH, Hesselkilde EM, Kjeldsen ST, Hopster-Iversen C, D'Souza A, Jespersen T, Buhl R.
(2023).
Muscarinic acetylcholine receptors M2 are upregulated in the atrioventricular nodal tract in horses with a high burden of second-degree atrioventricular block.
Front Cardiovasc Med, 10, 1102164.
https://doi.org/10.3389/fcvm.2023.1102164 Publication
Researcher Affiliations
- Laboratory of Cardiac Physiology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- Laboratory of Cardiac Physiology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- Institute of Pharmacology, West German Heart and Vascular Centre, University Duisburg-Essen, Essen, Germany.
- Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
- Core Facility for Integrated Microscopy, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- Laboratory of Cardiac Physiology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
- Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
- Division of Cardiovascular Sciences, University of Manchester, 3.30 Core Technology, Manchester, United Kingdom.
- Laboratory of Cardiac Physiology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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