Down-regulation of L-type calcium channel and sarcoplasmic reticular Ca2+-ATPase mRNA in human atrial fibrillation without significant change in the mRNA of ryanodine receptor, calsequestrin and phospholamban -: An insight into the mechanism of atrial electrical remodeling

OBJECTIVES We investigated the gene expression of calcium-handling genes including L-type calcium channel, sarcoplasmic reticular calcium adenosine triphosphatase (Ca2+-ATPase), ryanodine receptor, calsequestrin and phospholamban in human atrial fibrillation. BACKGROUND Recent studies have demonstrated that atrial electrical remodeling in atrial fibrillation is associated with intracellular calcium overload. However, the changes of calcium-handling proteins remain unclear. METHODS A total of 34 patients undergoing open heart surgery were included. Atrial tissue was obtained from the right atrial free wall, right atrial appendage, left atrial free wall and left atrial appendage, respectively. The messenger ribonucleic acid (mRNA) amount of the genes was measured by reverse transcription-polymerase chain reaction and normalized to the mRNA levels of glyceraldehyde 3-phosphate dehydrogenase. RESULTS The mRNA of L-type calcium channel and of Ca2+-ATPase was significantly decreased in patients with persistent atrial fibrillation for more than 3 months (0.36 +/- 0.26 vs. 0.90 +/- 0.88 for L-type calcium channel; 0.69 +/- 0.42 vs. 1.21 +/- 0.68 for Ca2+-ATPase; both p < 0.05, all data in arbitrary unit). We further demonstrated that there nas no spatial dispersion of the gene expression among the four atrial tissue sampling sites. Age, gender and underlying cardiac disease had no significant effects on the gene expression. In contrast, the mRNA levels of ryanodine receptor, calsequestrin and phospholamban showed no significant change in atrial fibrillation. CONCLUSIONS L-type calcium channel and the sarcoplasmic reticular Ca2+-ATPase gene were downregulated in atrial fibrillation. These changes may be a consequence of, as well as a contributory factor for, atrial fibrillation. (C) 1999 by the American College of Cardiology.