Alterations in Cardiac Sarcoplasmic Reticulum Ca^<2+> Regulatory proteins in the atrial tissue of patients with chronic atrial fibrilla

Background Clinically, atrial fibrillation (AF) is the most frequently encountered arrhythmia. Recent studies indicate that an inability to maintain intracellular Ca^<2+> homeostasis with a consequent increase in membrane-triggered activity could be the primary initiating factor in some circumstances, and that cytosolic Ca^<2+> abnormalities are an important mediator of sustained AF. Objectives The purpose of this study was to determine whether AF patients have alterations in the SR Ca^<2+> regulatory proteins in the atrial myocardium. Methods and Results We measured the maximum number of [^3H] ryanodine binding sites (Bmax) and the expression levels of ryanodine receptor (RyR) mRNA and Ca^<2+>-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). In AF patients: (i) 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, (ii) Bmax was significantly lower in the left atrium than in the right atrium, (iii) Bmax in the left atrium was significantly lower at higher levels of pulmonary capillary wedge pressure, (iv) the expression level of RyR mRNA was significantly lower in both the left (1.24x10^<-2>±1.28x10^<-2>) and right (1.70x10^<-2>±1.78x10^<-2>) atrium than in the right atrium of NSR patients (6.11x10^<-2>±2.79x10^<-2>), and (v) the expression level of Ca^<2+>-ATPase mRNA was significantly lower in both the left (5.67x10^<-2>±4.01x10^<-2>) and right (7.71x10^<-2>±3.56x10^<-2>) atrium than in the right atrium (12.60x10^<-2>±3.92x10^<-2>) of NSR patients.Conclusions These results may suggest that, in the patients with chronic AF due to MVD, mechanical overload of the atrial myocardium decreases Bmax for RyRs and the expression of both RyR mRNA and Ca^<2+>-ATPase mRNA. This might result in abnormal intracellular Ca^<2+> handling and alter the electrophysiologic properties of the atrium, leading to the initiation and maintenance of AF.

慢性心房細動

心筋筋小胞体

リアノジンレセプター

Ca^<2+>-ATPase

本文データは山口大学医学会の許諾に基づきCiNiiから複製したものである