Mechanical stretch of atrial myocyte monolayer decreases sarcoplasmic reticulum calcium adenosine triphosphatase expression and increases susceptibility to repolarization alternans

Chia Ti Tsai, Fu Tien Chiang, Chuen Den Tseng, Chih Chieh Yu, Yi Chih Wang, Ling Ping Lai, Juey Jen Hwang, Jiunn Lee Lin

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2106-2115
Number of pages10
JournalJournal of the American College of Cardiology
Volume58
Issue number20
DOIs
Publication statusPublished - Nov 8 2011
Externally publishedYes

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pamidronate
Calcium-Transporting ATPases
Sarcoplasmic Reticulum
Muscle Cells
Atrial Fibrillation
Calcium
Action Potentials
Adenosine Triphosphatases
Premature Cardiac Complexes
Optical Devices
Heart Valve Diseases
Ventricular Fibrillation
Silicones
Heart Failure
Hypertension
Membranes

Keywords

  • atrial fibrillation
  • atrial myocyte culture
  • optical mapping
  • repolarization alternans

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Mechanical stretch of atrial myocyte monolayer decreases sarcoplasmic reticulum calcium adenosine triphosphatase expression and increases susceptibility to repolarization alternans. / Tsai, Chia Ti; Chiang, Fu Tien; Tseng, Chuen Den; Yu, Chih Chieh; Wang, Yi Chih; Lai, Ling Ping; Hwang, Juey Jen; Lin, Jiunn Lee.

In: Journal of the American College of Cardiology, Vol. 58, No. 20, 08.11.2011, p. 2106-2115.

Research output: Contribution to journalArticle

Tsai, Chia Ti ; Chiang, Fu Tien ; Tseng, Chuen Den ; Yu, Chih Chieh ; Wang, Yi Chih ; Lai, Ling Ping ; Hwang, Juey Jen ; Lin, Jiunn Lee. / Mechanical stretch of atrial myocyte monolayer decreases sarcoplasmic reticulum calcium adenosine triphosphatase expression and increases susceptibility to repolarization alternans. In: Journal of the American College of Cardiology. 2011 ; Vol. 58, No. 20. pp. 2106-2115.
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T1 - Mechanical stretch of atrial myocyte monolayer decreases sarcoplasmic reticulum calcium adenosine triphosphatase expression and increases susceptibility to repolarization alternans

AU - Tsai, Chia Ti

AU - Chiang, Fu Tien

AU - Tseng, Chuen Den

AU - Yu, Chih Chieh

AU - Wang, Yi Chih

AU - Lai, Ling Ping

AU - Hwang, Juey Jen

AU - Lin, Jiunn Lee

PY - 2011/11/8

Y1 - 2011/11/8

N2 - 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.

AB - 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.

KW - atrial fibrillation

KW - atrial myocyte culture

KW - optical mapping

KW - repolarization alternans

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