Alterations in cardiac sarcoplasmic reticulum Ca2+regulatory proteins in the atrial tissue of patients with chronic atrial fibrillation

T Ohkusa, T Ueyama, J Yamada, M Yano… - Journal of the American …, 1999 - jacc.org
T Ohkusa, T Ueyama, J Yamada, M Yano, Y Fujumura, K Esato, M Matsuzaki
Journal of the American College of Cardiology, 1999jacc.org
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 …
Abstract
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 × 10−2± 1.28 × 10−2) and right (1.70 × 10−2± 1.78 × 10−2) atrium than in the right atrium of NSR patients (6.11 × 10−2± 2.79 × 10−2); and 5) the expression level of Ca2+-ATPase mRNA was significantly lower in both the left (5.67 × 10−2± 4.01 × 10−2) and right (7.71 × 10−2± 3.56 × 10−2) atrium than in the right atrium (12.60 × 10−2± 3.92 × 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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