Hi all,
I appreciate if someone could explain the mechanisms associated with the relief of inhibitory effects of phospholamban on cardiac calcium pump SERCA2a through the phosphorylation of phospholamban by PKA or CaMKII? Thank you so much
Hello Nghiem. You would be better served looking in a textbook or review article. There is not much space here to give a detailed answer. Briefly, Phospholamban and SERCA are located in the cardiac SR membrane. Phospholamban interacts with SERCA and inhibits SERCA activity. When phospholamban is phosphorylated by PKA (Ser16) or CaMKII (Thr17) a conformational change occurs in phospholamban such that it does not interact with SERCA - removing the inhibitory effect on SERCA activity. As a result, SERCA transports Ca2+ into the SR at a higher rate. The effect of this is 1) more rapid relaxation of the heart and 2) more calcium in the SR for release with the next heart beat, meaning a stronger contraction. Dephospho rylation of phospholamban re-establishes inhibition of SERCA.
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