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CLINICAL STUDIES

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

Ling-Ping Lai, MD^* , Ming-Jai Su, PhD^*, Jiunn-Lee Lin, MD, Fang-Yue Lin, MD, Chang-Her Tsai, MD, Yih-Sharng Chen, MD, Shoei K. Stephen Huang, MD, FACC, Yung-Zu Tseng, MD and Wen-Pin Lien, MD, FACC

^* Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan

Manuscript received July 7, 1998; revised manuscript received November 18, 1998, accepted December 24, 1998.

Reprint requests and correspondence: Dr. Ming-Jai Su, Pharmacological Institute, College of Medicine, National Taiwan University, No 1, Section 1, Jen-Ai Road, Taipei, Taiwan
mjsu{at}ha.mc.ntu.edu.tw

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 was 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 down-regulated in atrial fibrillation. These changes may be a consequence of, as well as a contributory factor for, atrial fibrillation.

Abbreviations and Acronyms   Ca2+-ATPase = calcium adenosine triphosphatase   cDNA = complementary deoxyribonucleic acid   GAPDH = glyceraldehyde 3-phosphate dehydrogenase   ICa = ionized calcium   mRNA = messenger ribonucleic acid

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