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

Cite this

Brundel, B J ; Van Gelder, I C ; Henning, R H ; Tuinenburg, A E ; Wietses, M ; Grandjean, J G ; Wilde, A A ; Van Gilst, W H ; Crijns, H J. / 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. In: Journal of the American College of Cardiology. 2001 ; Vol. 37, No. 3. pp. 926-32.
@article{3768f6fd68764e548f5dfab19fce6a03,
title = "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",
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.",
keywords = "Aged, Aged, 80 and over, Atrial Fibrillation/physiopathology, Female, Gene Expression Regulation/physiology, Heart Atria/physiopathology, Humans, Male, Middle Aged, Potassium Channels/metabolism, Potassium Channels, Voltage-Gated, RNA, Messenger/analysis, Shal Potassium Channels, Ventricular Function, Left",
author = "Brundel, {B J} and {Van Gelder}, {I C} and Henning, {R H} and Tuinenburg, {A E} and M Wietses and Grandjean, {J G} and Wilde, {A A} and {Van Gilst}, {W H} and Crijns, {H J}",
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month = "3",
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language = "English",
volume = "37",
pages = "926--32",
journal = "Journal of the American College of Cardiology",
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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. / Brundel, B J; Van Gelder, I C; Henning, R H; Tuinenburg, A E; Wietses, M; Grandjean, J G; Wilde, A A; Van Gilst, W H; Crijns, H J.

In: Journal of the American College of Cardiology, Vol. 37, No. 3, 01.03.2001, p. 926-32.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Alterations in potassium channel gene expression in atria of patients with persistent and paroxysmal atrial fibrillation

T2 - differential regulation of protein and mRNA levels for K+ channels

AU - Brundel, B J

AU - Van Gelder, I C

AU - Henning, R H

AU - Tuinenburg, A E

AU - Wietses, M

AU - Grandjean, J G

AU - Wilde, A A

AU - Van Gilst, W H

AU - Crijns, H J

PY - 2001/3/1

Y1 - 2001/3/1

N2 - 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.

AB - 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.

KW - Aged

KW - Aged, 80 and over

KW - Atrial Fibrillation/physiopathology

KW - Female

KW - Gene Expression Regulation/physiology

KW - Heart Atria/physiopathology

KW - Humans

KW - Male

KW - Middle Aged

KW - Potassium Channels/metabolism

KW - Potassium Channels, Voltage-Gated

KW - RNA, Messenger/analysis

KW - Shal Potassium Channels

KW - Ventricular Function, Left

M3 - Article

VL - 37

SP - 926

EP - 932

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 3

ER -