TY - JOUR

T1 - The inter-chamber differences in the contractile function between left and right atrial cardiomyocytes in atrial fibrillation in rats

AU - Butova, Xenia

AU - Myachina, Tatiana

AU - Simonova, Raisa

AU - Kochurova, Anastasia

AU - Mukhlynina, Elena

AU - Kopylova, Galina

AU - Shchepkin, Daniil

AU - Khokhlova, Anastasia

N1 - 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.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

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U2 - 10.3389/fcvm.2023.1203093

DO - 10.3389/fcvm.2023.1203093

M3 - Article

VL - 10

JO - Frontiers in Cardiovascular Medicine

JF - Frontiers in Cardiovascular Medicine

SN - 2297-055X

M1 - 1203093

ER -