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Ablation of sarcolipin results in atrial remodeling

Ablation of sarcolipin results in atrial remodeling Sarcolipin (SLN) is a key regulator of sarco(endo)plasmic reticulum (SR) Ca 2+ -ATPase (SERCA), and its expression is altered in diseased atrial myocardium. To determine the precise role of SLN in atrial Ca 2+ homeostasis, we developed a SLN knockout ( sln−/− ) mouse model and demonstrated that ablation of SLN enhances atrial SERCA pump activity. The present study is designed to determine the long-term effects of enhanced SERCA activity on atrial remodeling in the sln−/− mice. Calcium transient measurements show an increase in atrial SR Ca 2+ load and twitch Ca 2+ transients. Patch-clamping experiments demonstrate activation of the forward mode of sodium/calcium exchanger, increased L-type Ca 2+ channel activity, and prolongation of action potential duration at 90% repolarization in the atrial myocytes of sln−/− mice. Spontaneous Ca 2+ waves, delayed afterdepolarization, and triggered activities are frequent in the atrial myocytes of sln−/− mice. Furthermore, loss of SLN in atria is associated with increased interstitial fibrosis and altered expression of genes encoding collagen and other extracellular matrix proteins. Our results also show that the sln−/− mice are susceptible to atrial arrhythmias upon aging. Together, these findings indicate that ablation of SLN results in increased SERCA activity and SR Ca 2+ load, which, in turn, could cause abnormal intracellular Ca 2+ handling and atrial remodeling. fibrosis action potential duration calcium sarcoplasmic reticulum Ca 2+ adenosinetriphosphatase arrhythmias Copyright © 2012 the American Physiological Society « Previous | Next Article » Table of Contents This Article Published online before print April 11, 2012 , doi: 10.​1152/​ajpcell.​00425.​2011 Am J Physiol Cell Physiol June 15, 2012 vol. 302 no. 12 C1762-C1771 » Abstract Free Full Text Free to you Full Text (PDF) Free to you All Versions of this Article: ajpcell.00425.2011v1 302/12/C1762 most recent Classifications Article Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Citing articles via Web of Science Google Scholar Articles by Xie, L. H. Articles by Babu, G. J. PubMed PubMed citation Articles by Xie, L. H. Articles by Babu, G. J. Related Content Load related web page information Current Content June 15, 2012 Alert me to new issues of Am J Physiol Cell Physiol About the Journal Calls for Papers Information for Authors Submit a Manuscript Ethical Policies AuthorChoice PubMed Central Policy Reprints and Permissions Advertising Press Copyright © 2012 the American Physiological Society Print ISSN: 0363-6143 Online ISSN: 1522-1563 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); try { var pageTracker = _gat._getTracker("UA-2924550-1"); pageTracker._trackPageview(); } catch(err) {} var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); try { var pageTracker = _gat._getTracker("UA-189672-30"); pageTracker._setDomainName(".physiology.org"); pageTracker._trackPageview(); } catch(err) {} http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Cell Physiology The American Physiological Society

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References (57)

Publisher
The American Physiological Society
Copyright
Copyright © 2012 the American Physiological Society
ISSN
0363-6143
eISSN
1522-1563
DOI
10.1152/ajpcell.00425.2011
pmid
22496245
Publisher site
See Article on Publisher Site

Abstract

Sarcolipin (SLN) is a key regulator of sarco(endo)plasmic reticulum (SR) Ca 2+ -ATPase (SERCA), and its expression is altered in diseased atrial myocardium. To determine the precise role of SLN in atrial Ca 2+ homeostasis, we developed a SLN knockout ( sln−/− ) mouse model and demonstrated that ablation of SLN enhances atrial SERCA pump activity. The present study is designed to determine the long-term effects of enhanced SERCA activity on atrial remodeling in the sln−/− mice. Calcium transient measurements show an increase in atrial SR Ca 2+ load and twitch Ca 2+ transients. Patch-clamping experiments demonstrate activation of the forward mode of sodium/calcium exchanger, increased L-type Ca 2+ channel activity, and prolongation of action potential duration at 90% repolarization in the atrial myocytes of sln−/− mice. Spontaneous Ca 2+ waves, delayed afterdepolarization, and triggered activities are frequent in the atrial myocytes of sln−/− mice. Furthermore, loss of SLN in atria is associated with increased interstitial fibrosis and altered expression of genes encoding collagen and other extracellular matrix proteins. Our results also show that the sln−/− mice are susceptible to atrial arrhythmias upon aging. Together, these findings indicate that ablation of SLN results in increased SERCA activity and SR Ca 2+ load, which, in turn, could cause abnormal intracellular Ca 2+ handling and atrial remodeling. fibrosis action potential duration calcium sarcoplasmic reticulum Ca 2+ adenosinetriphosphatase arrhythmias Copyright © 2012 the American Physiological Society « Previous | Next Article » Table of Contents This Article Published online before print April 11, 2012 , doi: 10.​1152/​ajpcell.​00425.​2011 Am J Physiol Cell Physiol June 15, 2012 vol. 302 no. 12 C1762-C1771 » Abstract Free Full Text Free to you Full Text (PDF) Free to you All Versions of this Article: ajpcell.00425.2011v1 302/12/C1762 most recent Classifications Article Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Citing articles via Web of Science Google Scholar Articles by Xie, L. H. Articles by Babu, G. J. PubMed PubMed citation Articles by Xie, L. H. Articles by Babu, G. J. Related Content Load related web page information Current Content June 15, 2012 Alert me to new issues of Am J Physiol Cell Physiol About the Journal Calls for Papers Information for Authors Submit a Manuscript Ethical Policies AuthorChoice PubMed Central Policy Reprints and Permissions Advertising Press Copyright © 2012 the American Physiological Society Print ISSN: 0363-6143 Online ISSN: 1522-1563 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); try { var pageTracker = _gat._getTracker("UA-2924550-1"); pageTracker._trackPageview(); } catch(err) {} var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); try { var pageTracker = _gat._getTracker("UA-189672-30"); pageTracker._setDomainName(".physiology.org"); pageTracker._trackPageview(); } catch(err) {}

Journal

AJP - Cell PhysiologyThe American Physiological Society

Published: Jun 15, 2012

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