The inter-chamber differences in the contractile function between left and right atrial cardiomyocytes in atrial fibrillation in rats

Xenia Butova; Tatiana Myachina; Raisa Simonova; Anastasia Kochurova; Elena Mukhlynina; Galina Kopylova; Daniil Shchepkin; Anastasia Khokhlova

doi:10.3389/fcvm.2023.1203093

The inter-chamber differences in the contractile function between left and right atrial cardiomyocytes in atrial fibrillation in rats

Front Cardiovasc Med. 2023 Aug 7:10:1203093. doi: 10.3389/fcvm.2023.1203093. eCollection 2023.

Authors

Xenia Butova¹, Tatiana Myachina¹, Raisa Simonova¹, Anastasia Kochurova¹, Elena Mukhlynina^{1

2}, Galina Kopylova¹, Daniil Shchepkin^{1

2}, Anastasia Khokhlova^{1

3}

Affiliations

¹ Institute of Immunology and Physiology, Ural Branch of Russian Academy of Sciences, Yekaterinburg, Russian Federation.
² Institute of Natural Sciences and Mathematics, Ural Federal University, Yekaterinburg, Russian Federation.
³ Institute of Physics and Technology, Ural Federal University, Yekaterinburg, Russian Federation.

Abstract

Introduction: The left and right atria (LA, RA) work under different mechanical and metabolic environments that may cause an intrinsic inter-chamber diversity in structure and functional properties between atrial cardiomyocytes (CM) in norm and provoke their different responsiveness to pathological conditions. In this study, we assessed a LA vs. RA difference in CM contractility in paroxysmal atrial fibrillation (AF) and underlying mechanisms.

Methods: We investigated the contractile function of single isolated CM from LA and RA using a 7-day acetylcholine (ACh)-CaCl₂ AF model in rats. We compared auxotonic force, sarcomere length dynamics, cytosolic calcium ([Ca²⁺]_i) transients, intracellular ROS and NO production in LA and RA CM, and analyzed the phosphorylation levels of contractile proteins and actin-myosin interaction using an in vitro motility assay.

Results: AF resulted in more prominent structural and functional changes in LA myocardium, reducing sarcomere shortening amplitude, and velocity of sarcomere relengthening in mechanically non-loaded LA CM, which was associated with the increased ROS production, decreased NO production, reduced myofibrillar content, and decreased phosphorylation of cardiac myosin binding protein C and troponin I. However, in mechanically loaded CM, AF depressed the auxotonic force amplitude and kinetics in RA CM, while force characteristics were preserved in LA CM.

Discussion: Thus, inter-atrial differences are increased in paroxysmal AF and affected by the mechanical load that may contribute to the maintenance and progression of AF.

Keywords: ([Ca2+]i) transients; actin-myosin interaction; atrial fibrillation; auxotonic force; left and right atria; protein phosphorylation; sarcomere shortening; single cardiomyocytes.

Grants and funding

This research was supported by the Russian Science Foundation #22-75-10134. The work was performed using the equipment of the Shared Research Center of Scientific Equipment of Institute of Immunology and Physiology. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.