Depletion of Ca2+ from the sarcoplasmic reticulum of cardiac muscle prompts phosphorylation of phospholamban to stimulate store refilling.
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.[1]References
- Depletion of Ca2+ from the sarcoplasmic reticulum of cardiac muscle prompts phosphorylation of phospholamban to stimulate store refilling. Bhogal, M.S., Colyer, J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
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