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

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 S100A...

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Published inGeneral physiology and biophysics Vol. 27; no. 2; p. 127
Main Authors Ackermann, G E, Domenighetti, A A, Deten, A, Bonath, I, Marenholz, I, Pedrazzini, T, Erne, P, Heizmann, C W
Format Journal Article
LanguageEnglish
Published Slovakia 01.06.2008
Subjects
Adrenergic alpha-Agonists - pharmacology
Adrenergic beta-Agonists - pharmacology
Animals
Dobutamine - pharmacology
Electrocardiography
Gene Expression Profiling
Heart - physiology
Heart Conduction System - drug effects
Isoproterenol - pharmacology
Mice
Mice, Knockout
Myocardium - metabolism
Norepinephrine - pharmacology
Oligonucleotide Array Sequence Analysis
S100 Proteins - genetics
S100 Proteins - physiology
Ventricular Function, Left - drug effects
Ventricular Pressure - drug effects
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Summary: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.
ISSN:0231-5882