S100A1: A regulator of myocardial contractility

Most, P. et al. (2001) S100A1: A regulator of myocardial contractility. Proceedings of the National Academy of Sciences of the United States of America, 98(24), pp. 13889-13894. (doi:10.1073/pnas.241393598)

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Abstract

S100A1, a Ca2+ 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 Ca2+ 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 Ca2+ cycling in S100A1-over-expressing cardiomyocytes revealed a significant increase in cytosolic Ca2+ transients, whereas in functional studies on saponin-permeabilized adult cardiomyocytes, the addition of S100A1 protein significantly enhanced SR Ca2+ uptake. Moreover, in Triton-skinned ventricular trabeculae, S100A1 protein significantly decreased myofibrillar Ca2+ sensitivity ([EC50%]) and Ca2+ 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 SIR Ca2+ handling and myofibrillar Ca2+ responsiveness.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Smith, Professor Godfrey
Authors: Most, P., Bernotat, J., Ehlermann, P., Pleger, S., Reppel, M., Borries, M., Niroomand, F., Pieske, B., Janssen, P., Eschenhagen, T., Karczewski, P., Smith, G., Koch, W., Katus, H., and Remppis, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences
Journal Name:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424

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