Alterations in cardiac sarcoplasmic reticulum Ca2+ regulatory proteins in the atrial tissue of patients with chronic atrial fibrillation.
OBJECTIVE
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.
Second Department of Internal Medicine, Yamaguchi University School of Medicine, Ube, Japan. ohkusa@po.cc.yamaguchi-u.ac.jp
T
T
Ohkusa
T
T
Ueyama
J
J
Yamada
M
M
Yano
Y
Y
Fujumura
K
K
Esato
M
M
Matsuzaki
D000368:Aged; D001281:Atrial Fibrillation / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D002908:Chronic Disease; D005260:Female; D006325:Heart Atria / Q000378:metabolism; D006349:Heart Valve Diseases / Q000150:complications / Q000503:physiopathology; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008943:Mitral Valve; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D019837:Ryanodine Receptor Calcium Release Channel; D000252:Calcium-Transporting ATPases