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

B J Brundel, I C Van Gelder, R H Henning, A E Tuinenburg, M Wietses, J G Grandjean, A A Wilde, W H Van Gilst, H J Crijns

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)926-32
Number of pages7
JournalJournal of the American College of Cardiology
Volume37
Issue number3
Publication statusPublished - 1 Mar 2001

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