Document Detail


Differential expression of potassium channels and abnormal conduction in experimental tachycardia-induced heart failure.
MedLine Citation:
PMID:  22311348     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Heart failure causes electrophysiological changes in the heart. Downregulation of repolarizing K+-currents leads to a prolongation of the cardiac action potential. Nevertheless, little is known about the differential expression of atrial and ventricular K+-channels in the failing heart. Ten rabbits underwent progressive rapid right ventricular pacing for 30 days. Digitized ECGs and echocardiograms were obtained. Left ventricular and left atrial tissue was harvested and mRNA levels of BNP, Kv4.3, rERG, Kv1.5, and KvLQT1 were measured by real time PCR. Experimental heart failure was characterized by left ventricular dilatation (13 ± 1 mm vs. 9 ± 1, p < .001), depressed fractional shortening (25 ± 5% vs. 40 ± 4, p < .001), and left atrial remodeling with increased diameter (16 mm ± 2 vs. 12 ± 1, p = .002) and weight (1.3 g ± 0.2 vs. 0.5 ± 0.1, p = .01). A prolongation of P-wave (44 ± 5 ms vs. 40 ± 4, p = .001) and PQ-interval (73 ± 10 ms vs. 66 ± 9, p = .009) occurred. In heart failure, BNP mRNA levels showed a significant upregulation in the left ventricle and atrium (1.83 AU ±1.31 vs. 0.67 ± 0.65, p < .05 and 7.16 AU ±1.76 vs. 0.77 ± 0.48, p < .05). Left ventricular Kv1.5 mRNA was reduced by 50% (p < .001) and KvLQT1 was reduced by 70% (p < .001). rERG and Kv4.3 mRNA were unchanged (n = ns). In contrast, left atrial Kv4.3 and KvLQT1 were reduced by 70% (p < .001), whereas rERG and Kv1.5 were unchanged (p = ns). Significant correlations were present between BNP and K+-channel expressions. Heart failure is characterized by significant changes in the gene expression of repolarizing K+-currents with a differential atrial and ventricular pattern. These molecular changes occur together with changes in cardiac function, geometry, conduction, and BNP expression and provide a functional basis for electrical vulnerability in heart failure.
Authors:
Christoph Birner; Oliver Husser; Andreas Jeron; Munhie Rihm; Sabine Fredersdorf; Markus Resch; Peter Schmid; Dierk Endemann; Günter Riegger; Andreas Luchner
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-7
Journal Detail:
Title:  Naunyn-Schmiedeberg's archives of pharmacology     Volume:  -     ISSN:  1432-1912     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-2-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0326264     Medline TA:  Naunyn Schmiedebergs Arch Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, Franz-Josef-Strauss-Allee 11, D-93055, Regensburg, Germany, christoph.birner@klinik.uni-regensburg.de.
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