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Depletion of Ca2+ from the sarcoplasmic reticulum of cardiac muscle prompts phosphorylation of phospholamban to stimulate store refilling

Bhogal, M.S. and Colyer, J. (1998) Depletion of Ca2+ from the sarcoplasmic reticulum of cardiac muscle prompts phosphorylation of phospholamban to stimulate store refilling. Proceedings of the National Academy of Sciences, 95 (4). pp. 1484-1489. ISSN 0027-8424

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Abstract

Nonmuscle cells have almost ubiquitously evolved a mechanism to detect and prevent Ca(2+) store depletionstore operated calcium entry. No such mechanism has, as yet, been reported in cardiac myocytes. However, it is conceivable that such a mechanism may play an important role in cardiac Ca(2+) homeostasis to ensure the availability of sufficient stored Ca(2+) to maintain normal excitation contraction coupling. We present data that confirms the presence of a mechanism that is able to monitor the Ca(2+) load of the SR and initiate a signaling process to accelerate Ca(2+) uptake by the SR when store depletion is detected. Depletion of SR Ca(2+) activates a protein kinase, the principal SR substrate of which is phospholamban. Phosphorylation of this SR protein promotes Ca(2+) pump activity and therefore store refilling. Furthermore, a protein kinase activity associated with the SR that is inhibited by Ca(2+) ions has been identified. We have measured lumenal [Ca(2+)] by using a fluorescent Ca(2+) indicator and found that by initiating Ca(2+) uptake and increasing Ca(2+) load, we can inhibit the protein kinase activity associated with the SR. This confirms that a protein kinase, that is regulated by lumenal [Ca(2+)], has been identified and represents part of a previously unidentified signalling cascade. This local feedback mechanism would allow the myocyte to detect and prevent SR Ca(2+) load depletion

Item Type: Article
Copyright, Publisher and Additional Information: Copyright © 1998 by the National Academy of Sciences
Institution: The University of Leeds
Academic Units: The University of Leeds > Faculty of Biological Sciences (Leeds) > Institute of Membrane and Systems Biology (Leeds)
Depositing User: Sherpa Assistant
Date Deposited: 13 Mar 2006
Last Modified: 07 Jun 2014 11:44
Published Version: http://www.pnas.org/cgi/content/full/95/4/1484
Status: Published
Refereed: Yes
URI: http://eprints.whiterose.ac.uk/id/eprint/569

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