CLINICAL STUDY: ELECTROPHYSIOLOGY
Alterations in potassium channel gene expression in atria of patients with persistent and paroxysmal atrial fibrillation: differential regulation of protein and mRNA levels for K+ channels
Bianca J. J. M. Brundel, MSc*  ,
Isabelle C. Van Gelder, MD*,
Robert H. Henning, MD,
Anton E. Tuinenburg, MD*,
Mirian Wietses,
Jan G. Grandjean, MD ,
Arthur A. M. Wilde, MD ,
Wiek H. Van Gilst, PhD and
Harry J. G. M. Crijns, MD*
* Department of Cardiology, Thoraxcenter University Hospital Groningen, Groningen, The Netherlands
Department of Clinical Pharmacology, Thoraxcenter University Hospital Groningen, Groningen, The Netherlands
Department of Thoracic Surgery, Thoraxcenter University Hospital Groningen, Groningen, The Netherlands
Department of Cardiology, University of Amsterdam, Utrecht, The Netherlands
Manuscript received October 22, 1999;
revised manuscript received September 25, 2000,
accepted November 3, 2000.
Reprint requests and correspondence: Dr. Isabelle Van Gelder, Department of Cardiology Thoraxcenter, University Hospital Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands
I.C.van.Gelder{at}thorax.azg.nl
OBJECTIVES
Our purpose was to determine whether patients with persistent atrial fibrillation (AF) and patients with paroxysmal AF show alterations in potassium channel expression.
BACKGROUND
Persistent AF is associated with a sustained shortening of the atrial action potential duration and atrial refractory period. Underlying molecular changes have not been studied in humans. We investigated whether a changed gene expression of specific potassium channels is associated with these changes in patients with persistent AF and in patients with paroxysmal AF.
METHODS
Right atrial appendages were obtained from 8 patients with paroxysmal AF, 10 with persistent AF and 18 matched controls in sinus rhythm. All controls underwent coronary artery bypass surgery, whereas most AF patients underwent Cox’s MAZE surgery (atrial arrhythmia surgery to cure AF) (n = 12). All patients had normal left ventricular function. mRNA (ribonucleic acid) levels were measured by semiquantitative polymerase chain reaction and protein content by Western blotting.
RESULTS
mRNA levels of transient outward channel (Kv4.3), acetylcholine-dependent potassium channel (Kir3.4) and ATP-dependent potassium channel (Kir6.2) were reduced in patients with persistent AF (–35%, –47% and –36%, respectively, p < 0.05), whereas only Kv4.3 mRNA level was reduced in patients with paroxysmal AF (–29%, p = 0.03). No changes were found for Kv1.5 and HERG mRNA levels in either group. Protein levels of Kv4.3, Kv1.5 and Kir3.1 were reduced both in patients with persistent AF (–39%, –84% and –47%, respectively, p < 0.05) and in those with paroxysmal AF (–57%, –64%, and –40%, respectively, p < 0.05).
CONCLUSIONS
Persistent AF is accompanied by reductions in mRNA and protein levels of several potassium channels. In patients with paroxysmal AF these reductions were observed predominantly at the protein level and not at the mRNA level, suggesting a post-transcriptional regulation.
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Abbreviations and Acronyms
| | AF | = atrial fibrillation | | CABG | = coronary artery bypass surgery | | DNA | = deoxyribonucleic acid | | GAPDH | = glyceraldehyde-3-phosphate dehydrogenase | | HERG | = gene encoding rapid component of the delayed rectifier IKr | | Kir3.1 | = gene encoding part of the IKACh, together with IKir3.4 | | Kir3.4 | = gene encoding part of the IKACh, together with IKir3.1 | | Kir6.2 | = gene encoding part of the IKATP | | Kv1.5 | = gene encoding ultra rapid component of the delayed rectifier IKur | | Kv4.3 | = gene underlying calcium independent transient outward current ITo1 | | LV | = left ventricular, left ventricle | | NYHA | = New York Heart Association | | PCR | = polymerase chain reaction | | RNA | = ribonucleic acid | | SR | = sinus rhythm |
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