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

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 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) mRN and calcium-adenosine triphosphatase (Ca2+-ATPase) mRN 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 mRN 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 mRN 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.