Abstract:
:The sarco(endo)plasmic reticulum calcium ATPase (SERCA) is responsible for transporting calcium (Ca(2+)) from the cytosol into the lumen of the sarcoplasmic reticulum (SR) following muscular contraction. The Ca(2+) sequestering activity of SERCA facilitates muscular relaxation in both cardiac and skeletal muscle. There are more than 10 distinct isoforms of SERCA expressed in different tissues. SERCA2a is the primary isoform expressed in cardiac tissue, whereas SERCA1a is the predominant isoform expressed in fast-twitch skeletal muscle. The Ca(2+) sequestering activity of SERCA is regulated at the level of protein content and is further modified by the endogenous proteins phospholamban (PLN) and sarcolipin (SLN). Additionally, several novel mechanisms, including post-translational modifications and microRNAs (miRNAs) are emerging as integral regulators of Ca(2+) transport activity. These regulatory mechanisms are clinically relevant, as dysregulated SERCA function has been implicated in the pathology of several disease states, including heart failure. Currently, several clinical trials are underway that utilize novel therapeutic approaches to restore SERCA2a activity in humans. The purpose of this review is to examine the regulatory mechanisms of the SERCA pump, with a particular emphasis on the influence of exercise in preventing the pathological conditions associated with impaired SERCA function.
journal_name
Can J Physiol Pharmacoljournal_title
Canadian journal of physiology and pharmacologyauthors
Stammers AN,Susser SE,Hamm NC,Hlynsky MW,Kimber DE,Kehler DS,Duhamel TAdoi
10.1139/cjpp-2014-0463subject
Has Abstractpub_date
2015-10-01 00:00:00pages
843-54issue
10eissn
0008-4212issn
1205-7541journal_volume
93pub_type
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