Muscarinic acetylcholine receptors M 2 are upregulated in the atrioventricular nodal tract in horses with a high burden of second-degree atrioventricular block

• Published in: Frontiers in cardiovascular medicine 2023, Vol.10, p.1102164
• Main Authors: Nissen, Sarah Dalgas, Saljic, Arnela, Carstensen, Helena, Braunstein, Thomas Hartig, Hesselkilde, Eva Melis, Kjeldsen, Sofie Troest, Hopster-Iversen, Charlotte, D'Souza, Alicia, Jespersen, Thomas, Buhl, Rikke
• Format: Article
• Language: English
• ISSN: 2297-055X; 2297-055X
• DOI: 10.3389/fcvm.2023.1102164

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. 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. 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). The AV block group had a significantly longer PR interval (mean ± SD, 0.40 ± 0.05 s;