S100A1: A regulator of myocardial contractility

Item Type:	Article
Title:	S100A1: A regulator of myocardial contractility
Creators Name:	Most, P. and Bernotat, J. and Ehlermann, P. and Pleger, S.T. and Reppel, M. and Boerries, M. and Niroomand, F. and Pieske, B. and Janssen, P.M.L. and Eschenhagen, T. and Karczewski, P. and Smith, G.L. and Koch, W.J.K. and Katus, H.A. and Remppis, A.
Abstract:	S100A1, a Ca 2+ binding protein of the EF-hand type, is preferentially expressed in myocardial tissue and has been found to colocalize with the sarcoplasmic reticulum (SR) and the contractile filaments in cardiac tissue. Because S100A1 is known to modulate SR Ca 2+ handling in skeletal muscle, we sought to investigate the specific role of S100A1 in the regulation of myocardial contractility. To address this issue, we investigated contractile properties of adult cardiomyocytes as well as of engineered heart tissue after S100A1 adenoviral gene transfer. S100A1 gene transfer resulted in a significant increase of unloaded shortening and isometric contraction in isolated cardiomyocytes and engineered heart tissues, respectively. Analysis of intracellular Ca 2+ cycling in S100A1-over-expressing cardiomyocytes revealed a significant increase in cytosolic Ca 2+ transients, whereas in functional studies on saponin-permeabilized adult cardiomyocytes, the addition of S100A1 protein significantly enhanced SR Ca 2+ uptake. Moreover, in Triton-skinned ventricular trabeculae, S100A1 protein significantly decreased myofibrillar Ca 2+ sensitivity ([EC 50%]) and Ca 2+ cooperativity, whereas maximal isometric force remained unchanged. Our data suggest that S100A1 effects are cAMP independent because cellular cAMP levels and protein kinase A-dependent phosphorylation of phospholamban were not altered, and carbachol failed to suppress S100A1 actions. These results show that S100A1 overexpression enhances cardiac contractile performance and establish the concept of S100A1 as a regulator of myocardial contractility. S100A1 thus improves cardiac contractile performance both by regulating SR Ca 2+ handling and myofibrillar Ca 2+ responsiveness.
Keywords:	Calcium, Calcium-Binding Proteins, Calcium-Transporting ATPases, Cultured Cells, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, Gene Expression, Gene Transfer Techniques, Heart Ventricles, Intracellular Fluid, Isometric Contraction, Microfilaments, Myocardial Contraction, Myocardium, Rabbits, Recombinant Fusion Proteins, S100 Proteins, Sarcoplasmic Reticulum, Sarcoplasmic Reticulum Calcium-Transporting ATPases, Animals, Swine
Source:	Proceedings of the National Academy of Sciences of the United States of America
ISSN:	0027-8424
Publisher:	National Academy of Sciences
Volume:	98
Number:	24
Page Range:	13889-13894
Date:	1 January 2001
Official Publication:	https://doi.org/10.1073/pnas.241393598
PubMed:	View item in PubMed

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