Regulatory role of phospholamban in the efficiency of cardiac sarcoplasmic reticulum Ca2+ transport

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Regulatory role of phospholamban in the efficiency of cardiac sarcoplasmic reticulum Ca2+ transport. / Frank, K.; Tilgmann, C.; Shannon, T. R.; Bers, D. M.; Kranias, E. G.

In: Biochemistry, Vol. 39, No. 46, 21.11.2000, p. 14176-14182.

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Frank, K. ; Tilgmann, C. ; Shannon, T. R. ; Bers, D. M. ; Kranias, E. G. / Regulatory role of phospholamban in the efficiency of cardiac sarcoplasmic reticulum Ca2+ transport. In: Biochemistry. 2000 ; Vol. 39, No. 46. pp. 14176-14182.

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TY - JOUR

T1 - Regulatory role of phospholamban in the efficiency of cardiac sarcoplasmic reticulum Ca2+ transport

AU - Frank, K.

AU - Tilgmann, C.

AU - Shannon, T. R.

AU - Bers, D. M.

AU - Kranias, E. G.

PY - 2000/11/21

Y1 - 2000/11/21

N2 - Phospholamban is an inhibitor of the sarcoplasmic reticulum Ca2+ transport apparent affinity for Ca2+ 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 Ca2+-uptake and Ca2+-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 Ca2+ transport by ATP hydrolysis, appeared to increase with increasing [Ca2+] in wild-type hearts. However, in the phospholamban-deficient hearts, this ratio was constant, and it was similar to the value obtained at high [Ca2+] 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 Ca2+ 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 Ca2+ transport for Ca2+ and the efficiency of this transport system at low [Ca2+], both leading to prolonged relaxation in myocytes.

AB - Phospholamban is an inhibitor of the sarcoplasmic reticulum Ca2+ transport apparent affinity for Ca2+ 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 Ca2+-uptake and Ca2+-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 Ca2+ transport by ATP hydrolysis, appeared to increase with increasing [Ca2+] in wild-type hearts. However, in the phospholamban-deficient hearts, this ratio was constant, and it was similar to the value obtained at high [Ca2+] 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 Ca2+ 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 Ca2+ transport for Ca2+ and the efficiency of this transport system at low [Ca2+], both leading to prolonged relaxation in myocytes.

UR - http://www.scopus.com/inward/record.url?scp=0034700256&partnerID=8YFLogxK

U2 - 10.1021/bi001049k

DO - 10.1021/bi001049k

M3 - Article

VL - 39

SP - 14176

EP - 14182

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 46

ER -