Mechanical Stretch of Atrial Myocyte Monolayer Decreases Sarcoplasmic Reticulum Calcium Adenosine Triphosphatase Expression and Increases Susceptibility to Repolarization Alternans

Objectives The purpose of this study was to investigate the effect of stretch (the major risk factor for atrial fibrillation [AF]) on spatial and temporal alternations of action potential duration (APD-ALT) and calcium transient in cultured atrial myocyte monolayer. Background How rapid firings or p...

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Bibliographic Details
Published in:Journal of the American College of Cardiology 2011-11, Vol.58 (20), p.2106-2115
Main Authors: Tsai, Chia-Ti, MD, PhD, Chiang, Fu-Tien, MD, PhD, Tseng, Chuen-Den, MD, PhD, Yu, Chih-Chieh, MD, Wang, Yi-Chih, MD, Lai, Ling-Ping, MD, PhD, Hwang, Juey-Jen, MD, PhD, Lin, Jiunn-Lee, MD, PhD
Format: Article
Language:English
Subjects:
Action potential
Action Potentials
Adenosine
Animals
Arrhythmias, Cardiac - enzymology
Arrhythmias, Cardiac - etiology
atrial fibrillation
Atrial Function
atrial myocyte culture
Atrium
Biological and medical sciences
Calcium
Calcium (reticular)
Calcium - metabolism
Cardiac arrhythmia
Cardiology
Cardiology. Vascular system
Cardiovascular
Cell Line
Circuits
Computer simulation
Deoxyribonucleic acid
Diastole - physiology
DNA
Fibrillation
Gene mapping
Heart diseases
Heart failure
Hypertension
In Vitro Techniques
Internal Medicine
Kinetics
Mapping
Medical sciences
Mice
Mortality
Muscular system
Myocytes
Myocytes, Cardiac - physiology
optical mapping
Rats
Rats, Wistar
repolarization alternans
Restitution
Risk factors
Rodents
Sarcoplasmic reticulum
Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism
Silicones
Stress, Mechanical
Studies
Triphosphatase
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Summary:Objectives The purpose of this study was to investigate the effect of stretch (the major risk factor for atrial fibrillation [AF]) on spatial and temporal alternations of action potential duration (APD-ALT) and calcium transient in cultured atrial myocyte monolayer. Background How rapid firings or premature beats trigger AF is not completely understood. Discordant repolarization alternans, characterized by simultaneous prolongation and shortening of APD in different myocardial regions, is central to the genesis of ventricular fibrillation. We hypothesized that repolarization alternans also is central to the initiation of multiple re-entry circuits and AF. Methods Confluent HL-1 atrial myocyte monolayer with spontaneous depolarization was cultured in silicone membrane and subjected to mechanical stretch. Rapid field pacing was used to induce alternans. A high-resolution dual optical mapping system was used to record action potentials and calcium transients. Results High-rate pacing induced APD-ALT and calcium transient in atrial myocyte monolayer. Mechanical stretch significantly decreased the thresholds for APD-ALT and calcium transient. Mechanical stretch decreased the expression of sarcoplasmic reticulum adenosine triphosphatase 2, and thus slower calcium reuptake kinetics, which was responsible for the susceptibility to alternans. Mechanical stretch did not alter the APD restitution kinetics. Mechanical stretch also enhanced spatially discordant alternans. Overexpression of sarcoplasmic reticulum adenosine triphosphatase 2 reversed all the effects of stretch on susceptibility to alternans. In intact atrium, mechanical stretch also enhanced discordant alternans. Conclusions Mechanical stretch increased the susceptibility to alternans in atrial myocytes, which may explain the susceptibility to AF in conditions of atrial stretch, such as mitral valvular heart disease, heart failure, and hypertension.
ISSN:0735-1097
1558-3597
DOI:10.1016/j.jacc.2011.07.039