Alterations in Gene Expression of Proteins Involved in the Calcium Handling in Patients with Atrial Fibrillation


  • Presented in part al the congress of the American College of Cardiology, Anaheim, CA, March 17, 1997 and at the congress of the NASPH (North American Society of Pacing and Electrophysiology). New Orleans. LA, May 8, 1997.

  • Dr. Van Gelder was supported by Grant 94.014 of the Netherlands Heart Foundation, The Hague, The Netherlands and by a fellowship of the Interuniversity Cardiology Institute. The Netherlands. The study was supported by Grant 96.051 of the Netherlands Heart Foundation, The Hague. The Netherlands.

Address for correspondence: Isabella C. Van Gelder, M.D., Department of Cardiology. Thoraxcenter, University Hospital Groningen, P.O. Box 30.001. 9700 RB Groningen, The Netherlands. Fax: 31-50-3614391;


Gene Expression in Human Atrial Fibrillation. Introduction: Atrial fibrillation (AF) leads to a loss of atrial contraction within hours to days. During persistence of AF, cellular dedifferentiation and hypertrophy occur, eventually resulting in degenerative changes and cell death. Abnormalities in the calcium handling in response to tachycardia-induced intracellular calcium overload play a pivotal role in these processes.

Methods and Results: The purpose was to investigate the mRNA expression of proteins and ion channels influencing the calcium handling in patients with persistent AF. Right atrial appendages were obtained from 18 matched controls in sinus rhythm (group 1) and 18 patients with persistent AF undergoing elective cardiac surgery. Previous duration of AF was ≥ 6 months in 9 (group 2) and > 6 months in 9 patients (group 3). In a single semiquantitative polymerase chain reaction, the mRNA of interest and of glyceraldehydes-3-phosphate dehydrogenase, were coamplified and separated by gel electrophoresis. L-type calcium channel α, subunit mRNA content was inversely related to the duration of AF: −26% in group 2 compared to group 1 (P = 0.2), and −49% in group 3 compared to group 1 (P = 0.01). Inhibitory guanine nucleotide binding protein iα2 mRNA content was reduced in group 3 compared to group 1 (−30%, P = 0.01). Sarcoplasmic reticulum calcium ATPase, phospholamban and sodiumcalcium exchanger mRNA contents were not affected by AF.

Conclusions: AF-induced alterations in mRNA contents of proteins and ion channels involved in the calcium handling seem to occur in relation to the previous duration of AF. In the present patient population, these changes were significant only if AF lasted > 6 months.