Regulatory Role of Phospholamban in the Efficiency of Cardiac Sarcoplasmic Reticulum Ca super(2+) Transport

Phospholamban is an inhibitor of the sarcoplasmic reticulum Ca super(2+) transport apparent affinity for Ca super(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 super(2+)-uptake and Ca super(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 super(2+) transport by ATP hydrolysis, appeared to increase with increasing [Ca super(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 super(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 super(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 super(2+) transport for Ca super(2+) and the efficiency of this transport system at low [Ca super(2+)], both leading to prolonged relaxation in myocytes.