EXPERIMENTAL STUDIES
Alterations in cardiac sarcoplasmic reticulum Ca2+ regulatory proteins in the atrial tissue of patients with chronic atrial fibrillation
Tomoko Ohkusa, MD, PhD*,
Takeshi Ueyama, MD, PhD*,
Jutaro Yamada, MD*,
Masafumi Yano, MD, PhD*,
Yoshihiko Fujumura, MD, PhD ,
Kensuke Esato, MD, PhD and
Masunori Matsuzaki, MD, PhD, FACC*
* Second Department of Internal Medicine, Yamaguchi University School of Medicine, Ube, Yamaguchi, 755-8505, Japan
First Department of Surgery, Yamaguchi University School of Medicine, Ube, Yamaguchi, 755-8505, Japan
Manuscript received July 30, 1998;
revised manuscript received February 23, 1999,
accepted March 24, 1999.
Reprint requests and correspondence: Dr. Tomoko Ohkusa, Second Department of Internal Medicine, Yamaguchi University School of Medicine, 1144, Kogushi, Ube, Yamaguchi 755-8505, Japan
ohkusa{at}po.cc.yamaguchi-u.ac.jp
OBJECTIVES
Our purpose was to determine whether atrial fibrillation (AF) patients have alterations in sarcoplasmic reticulum (SR) Ca2+ regulatory proteins in the atrial myocardium.
BACKGROUND
Clinically, AF is the most frequently encountered arrhythmia. Recent studies indicate that an inability to maintain intracellular Ca2+ homeostasis with a consequent increase in membrane-triggered activity could be the primary initiating factor in some circumstances, and that cytosolic Ca2+ abnormalities are an important mediator of sustained AF.
METHODS
We measured the maximum number of [3H]ryanodine binding sites (Bmax) and the expression levels of ryanodine receptor (RyR) mRNA and calcium-adenosine triphosphatase (Ca2+-ATPase) mRNA in atrial myocardial tissue from 13 patients with AF due to mitral valvular disease (MVD) and 9 patients with normal sinus rhythm (NSR).
RESULTS
In AF patients, 1) Bmax was significantly lower in each atrium (0.21 ± 0.03 pmol/mg [right], 0.16 ± 0.04 pmol/mg [left]) than in the right atrium (0.26 ± 0.08 pmol/mg) of NSR patients; 2) Bmax was significantly lower in the left atrium than in the right atrium; 3) Bmax in the left atrium was significantly lower at higher levels of pulmonary capillary wedge pressure; 4) the expression level of RyR mRNA was significantly lower in both the left (1.24 x 10–2 ± 1.28 x 10–2) and right (1.70 x 10–2 ± 1.78 x 10–2) atrium than in the right atrium of NSR patients (6.11 x 10–2 ± 2.79 x 10–2); and 5) the expression level of Ca2+-ATPase mRNA was significantly lower in both the left (5.67 x 10–2 ± 4.01 x 10–2) and right (7.71 x 10–2 ± 3.56 x 10–2) atrium than in the right atrium (12.60 x 10–2 ± 3.92 x 10–2) of NSR patients.
CONCLUSIONS
These results provide the first direct evidence of abnormalities in the Ca2+ regulatory proteins of the atrial myocardium in chronic AF patients. Conceivably, such abnormalities may be involved in the initiation and/or perpetuation of AF.
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Abbreviations and Acronyms
| | AF | = atrial fibrillation | | Ca2+-ATPase | = calcium-adenosine triphosphatase | | mRNA | = messenger ribonucleic acid | | MVD | = mitral valvular disease | | NSR | = normal sinus rhythm | | RT-PCR | = reverse transcription–polymerase chain reaction | | RyR | = ryanodine receptor | | SR | = sarcoplasmic reticulum |
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