QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online January 14, 2005
doi: 10.1242/10.1242/jcs.01614

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Most, P. Articles by Schoenenberger, C.-A. Search for Related Content PubMed PubMed Citation Articles by Most, P. Articles by Schoenenberger, C.-A.

Distinct subcellular location of the Ca²⁺-binding protein S100A1 differentially modulates Ca²⁺-cycling in ventricular rat cardiomyocytes

Patrick Most^1,2,*, Melanie Boerries^3,*, Carmen Eicher^2,*, Christopher Schweda², Mirko Völkers², Thilo Wedel⁴, Stefan Söllner⁵, Hugo A. Katus², Andrew Remppis², Ueli Aebi³, Walter J. Koch¹ and Cora-Ann Schoenenberger^3,

¹ Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA
² Department of Internal Medicine III, Division of Cardiology, University of Heidelberg, 69115 Heidelberg, Germany
³ Maurice E. Mueller Institute, Biozentrum, University of Basel, 4056 Basel, Switzerland
⁴ Institute of Anatomy, University of Lübeck, 23538 Lübeck, Germany
⁵ Department of Plastic Surgery, University of Lübeck, 23538 Lübeck, Germany

Author for correspondence (e-mail: cora-ann.schoenenberger{at}unibas.ch, patrick.most{at}jefferson.edu)

Accepted 27 October 2004

Calcium is a key regulator of cardiac function and is modulated through the Ca²⁺-sensor protein S100A1. S100 proteins are considered to exert both intracellular and extracellular functions on their target cells. Here we report the impact of an increased intracellular S100A1 protein level on Ca²⁺-homeostasis in neonatal ventricular cardiomyocytes in vitro. Specifically, we compare the effects of exogenously added recombinant S100A1 to those resulting from the overexpression of a transduced S100A1 gene. Extracellularly added S100A1 enhanced the Ca²⁺-transient amplitude in neonatal ventricular cardiomyocytes (NVCMs) through a marked decrease in intracellular diastolic Ca²⁺-concentrations ([Ca²⁺]_i). The decrease in [Ca²⁺]_i was independent of sarcoplasmic reticulum Ca²⁺-ATPase (SERCA2a) activity and was probably the result of an increased sarcolemmal Ca²⁺-extrusion through the sodium-calcium exchanger (NCX). At the same time the Ca²⁺-content of the sarcoplasmic reticulum (SR) decreased. These effects were dependent on the uptake of extracellularly added S100A1 protein and its subsequent routing to the endosomal compartment. Phospholipase C and protein kinase C, which are tightly associated with this subcellular compartment, were found to be activated by endocytosed S100A1.

By contrast, adenoviral-mediated intracellular S100A1 overexpression enhanced the Ca²⁺-transient amplitude in NVCMs mainly through an increase in systolic [Ca²⁺]_i. The increased Ca²⁺-load in the SR was based on an enhanced SERCA2a activity while NCX function was unaltered. Overexpressed S100A1 colocalized with SERCA2a and other Ca²⁺-regulatory proteins at the SR, whereas recombinant S100A1 protein that had been endocytosed did not colocalize with SR proteins. This study provides the first evidence that intracellular S100A1, depending on its subcellular location, modulates cardiac Ca²⁺-turnover via different Ca²⁺-regulatory proteins.

Key words: S100A1, Sodium-calcium exchanger, SERCA2a, Calcium-cycling

This article has been cited by other articles:

				J. H. Boyd, B. Kan, H. Roberts, Y. Wang, and K. R. Walley S100A8 and S100A9 Mediate Endotoxin-Induced Cardiomyocyte Dysfunction via the Receptor for Advanced Glycation End Products Circ. Res., May 23, 2008; 102(10): 1239 - 1246. [Abstract] [Full Text] [PDF]

				P. Most, A. Remppis, S. T. Pleger, H. A. Katus, and W. J. Koch S100A1: a novel inotropic regulator of cardiac performance. Transition from molecular physiology to pathophysiological relevance Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2007; 293(2): R568 - R577. [Abstract] [Full Text] [PDF]

				M. Boerries, P. Most, J. R. Gledhill, J. E. Walker, H. A. Katus, W. J. Koch, U. Aebi, and C.-A. Schoenenberger Ca2+-Dependent Interaction of S100A1 with F1-ATPase Leads to an Increased ATP Content in Cardiomyocytes Mol. Cell. Biol., June 15, 2007; 27(12): 4365 - 4373. [Abstract] [Full Text] [PDF]

				K. Guan, S. Wagner, B. Unsold, L. S. Maier, D. Kaiser, B. Hemmerlein, K. Nayernia, W. Engel, and G. Hasenfuss Generation of Functional Cardiomyocytes From Adult Mouse Spermatogonial Stem Cells Circ. Res., June 8, 2007; 100(11): 1615 - 1625. [Abstract] [Full Text] [PDF]

				S. T. Pleger, P. Most, M. Boucher, S. Soltys, J. K. Chuprun, W. Pleger, E. Gao, A. Dasgupta, G. Rengo, A. Remppis, et al. Stable Myocardial-Specific AAV6-S100A1 Gene Therapy Results in Chronic Functional Heart Failure Rescue Circulation, May 15, 2007; 115(19): 2506 - 2515. [Abstract] [Full Text] [PDF]

				P. Most, H. Seifert, E. Gao, H. Funakoshi, M. Volkers, J. Heierhorst, A. Remppis, S. T. Pleger, B. R. DeGeorge Jr, A. D. Eckhart, et al. Cardiac S100A1 Protein Levels Determine Contractile Performance and Propensity Toward Heart Failure After Myocardial Infarction Circulation, September 19, 2006; 114(12): 1258 - 1268. [Abstract] [Full Text] [PDF]

				M. Reppel, P. Sasse, R. Piekorz, M. Tang, W. Roell, Y. Duan, A. Kletke, J. Hescheler, B. Nurnberg, and B. K. Fleischmann S100A1 Enhances the L-type Ca2+ Current in Embryonic Mouse and Neonatal Rat Ventricular Cardiomyocytes J. Biol. Chem., October 28, 2005; 280(43): 36019 - 36028. [Abstract] [Full Text] [PDF]