Document Detail

Molecular remodeling of Kv4.3 potassium channels in human atrial fibrillation.
MedLine Citation:
PMID:  10868735     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: Atrial fibrillation (AF) is associated with important alterations in cardiac ion channels that cause shortening and impaired rate adaptation of atrial repolarization. The mechanisms underlying potassium current remodeling in human AF are not clear. We investigated the effects of AF on the gene expression of the Kv4.3, Kv1.4, and Kv1.5 potassium channel subunits and correlated the findings with the transient outward (Ito) and the sustained outward (Isus or I(Kur)) potassium current. METHODS AND RESULTS: Semiquantitative reverse transcription-polymerase chain reaction was used to evaluate mRNA expression, and ion currents were studied with the patch clamp technique in right atrial appendages from patients in AF and compared with those from patients in stable sinus rhythm (SR). The presence of AF was associated with a 61% reduction in Kv4.3 mRNA expression (P < 0.001 vs SR), which was paralleled by a reduction in Ito current densities in this group of patients (i.e., at +50 mV: 7.44+/-0.76 pA/pF in SR and 1.24+/-0.28 pA/pF in AF; P < 0.001 vs SR). mRNA levels of Kv1.4 were identical in the two groups. AF did not affect either the gene expression of Kv1.5 or the current densities of Isus. CONCLUSION: Chronic AF in humans reduces Ito by transcriptional down-regulation of the Kv4.3 potassium channel. Altered gene expression is an important component of the electrical remodeling process and may contribute to repolarization abnormalities in AF.
J B Grammer; R F Bosch; V Kühlkamp; L Seipel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular electrophysiology     Volume:  11     ISSN:  1045-3873     ISO Abbreviation:  J. Cardiovasc. Electrophysiol.     Publication Date:  2000 Jun 
Date Detail:
Created Date:  2000-10-19     Completed Date:  2000-10-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9010756     Medline TA:  J Cardiovasc Electrophysiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  626-33     Citation Subset:  IM    
Department of Pharmacology, University of Tübingen, Germany.
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MeSH Terms
Atrial Fibrillation / metabolism*,  pathology
Atrial Function
Electric Conductivity
Heart Rate
Kv1.4 Potassium Channel
Kv1.5 Potassium Channel
Middle Aged
Myocardium / metabolism,  pathology
Patch-Clamp Techniques
Potassium / physiology
Potassium Channels / genetics,  metabolism*,  physiology
Potassium Channels, Voltage-Gated*
RNA, Messenger / metabolism
Reference Values
Shal Potassium Channels
Reg. No./Substance:
0/KCNA4 protein, human; 0/KCNA5 protein, human; 0/KCND3 protein, human; 0/Kv1.4 Potassium Channel; 0/Kv1.5 Potassium Channel; 0/Potassium Channels; 0/Potassium Channels, Voltage-Gated; 0/RNA, Messenger; 0/Shal Potassium Channels; 7440-09-7/Potassium

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