Depletion of Ca2+ from the sarcoplasmic reticulum of cardiac muscle prompts phosphorylation of phospholamban to stimulate store refilling
AUTOR(ES)
Bhogal, Moninder Singh
FONTE
The National Academy of Sciences
RESUMO
Nonmuscle cells have almost ubiquitously evolved a mechanism to detect and prevent Ca2+ store depletion—store 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 Ca2+ homeostasis to ensure the availability of sufficient stored Ca2+ to maintain normal excitation contraction coupling. We present data that confirms the presence of a mechanism that is able to monitor the Ca2+ load of the SR and initiate a signaling process to accelerate Ca2+ uptake by the SR when store depletion is detected. Depletion of SR Ca2+ activates a protein kinase, the principal SR substrate of which is phospholamban. Phosphorylation of this SR protein promotes Ca2+ pump activity and therefore store refilling. Furthermore, a protein kinase activity associated with the SR that is inhibited by Ca2+ ions has been identified. We have measured lumenal [Ca2+] by using a fluorescent Ca2+ indicator and found that by initiating Ca2+ uptake and increasing Ca2+ load, we can inhibit the protein kinase activity associated with the SR. This confirms that a protein kinase, that is regulated by lumenal [Ca2+], 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 Ca2+ load depletion.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=19055Documentos Relacionados
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