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S100A1 deficiency results in prolonged ventricular repolarization in response to sympathetic activation

Item Type:Article
Title:S100A1 deficiency results in prolonged ventricular repolarization in response to sympathetic activation
Creators Name:Ackermann, G.E. and Domenighetti, A.A. and Deten, A. and Bonath, I. and Marenholz, I. and Pedrazzini, T. and Erne, P. and Heizmann, C.W.
Abstract:S100A1 is a Ca(2+)-binding protein and predominantly expressed in the heart. We have generated a mouse line of S100A1 deficiency by gene trap mutagenesis to investigate the impact of S100A1 ablation on heart function. Electrocardiogram recordings revealed that after beta-adrenergic stimulation S100A1-deficient mice had prolonged QT, QTc and ST intervals and intraventricular conduction disturbances reminiscent of 2 : 1 bundle branch block. In order to identify genes affected by the loss of S100A1, we profiled the mutant and wild type cardiac transcriptomes by gene array analysis. The expression of several genes functioning to the electrical activity of the heart were found to be significantly altered. Although the default prediction would be that mRNA and protein levels are highly correlated, comprehensive immunoblot analyses of salient up- or down-regulated candidate genes of any cellular network revealed no significant changes on protein level. Taken together, we found that S100A1 deficiency results in cardiac repolarization delay and alternating ventricular conduction defects in response to sympathetic activation accompanied by a significantly different transcriptional regulation.
Keywords:S100A1, Genetically Altered Mice, Heart, QT and ST Intervals, Transcriptome Profiling, Animals, Mice
Source:General Physiology and Biophysics
Publisher:R and D Print
Page Range:127-142
Date:June 2008
Official Publication:http://www.elis.sk/index.php?page=shop.product_details&flypage=flypage.tpl&product_id=663&category_id=29&option=com_virtuemart&vmcchk=1&Itemid=1
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