Document Detail


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.
MedLine Citation:
PMID:  11693772     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  37     ISSN:  0735-1097     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2001 Mar 
Date Detail:
Created Date:  2001-11-05     Completed Date:  2001-12-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  926-32     Citation Subset:  AIM; IM    
Affiliation:
Department of Cardiology, Thoraxcenter University Hospital Groningen, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
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
Chemical
Reg. No./Substance:
0/KCND3 protein, human; 0/Potassium Channels; 0/Potassium Channels, Voltage-Gated; 0/RNA, Messenger; 0/Shal Potassium Channels

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