Dephosphorylated phospholamban decreases the apparent affinity and efficiency of sarcoplasmic reticulum Ca(2+) transport at low [Ca(2+)], leading to prolonged myocyte relaxation.
Phospholamban is an inhibitor of the sarcoplasmic reticulum Ca(2+) transport apparent affinity for Ca(2+) in cardiac muscle. This inhibitory effect of phospholamban can be relieved through its phosphorylation or ablation. To better characterize the regulatory mechanism of phospholamban, we examined the initial rates of Ca(2+)-uptake and Ca(2+)-ATPase activity under identical conditions, using sarcoplasmic reticulum-enriched preparations from phospholamban-deficient and wild-type hearts. The apparent coupling ratio, calculated by dividing the initial rates of Ca(2+) transport by ATP hydrolysis, appeared to increase with increasing Ca(2+) in wild-type hearts. However, in the phospholamban-deficient hearts, this ratio was constant, and it was similar to the value obtained at high Ca(2+) in wild-type hearts. Phosphorylation of phospholamban by the catalytic subunit of protein kinase A in wild-type sarcoplasmic reticulum also resulted in a constant value of the apparent ratio of Ca(2+) transported per ATP hydrolyzed, which was similar to that present in phospholamban-deficient hearts. Thus, the inhibitory effects of dephosphorylated phospholamban involve decreases in the apparent affinity of sarcoplasmic reticulum Ca(2+) transport for Ca(2+) and the efficiency of this transport system at low Ca(2+), both leading to prolonged relaxation in myocytes.
Frank et al. (Sat,) studied this question.
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